杭州市区人群主观乳糖不耐受流行病学调查及乳糖酶基因多态性研究
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摘要
1杭州市区人群主观乳糖不耐受流行病学调查
1.1杭州市区人群乳糖不耐受发生率调查及相关因素分析
背景:由于乳糖酶的缺乏,很多人群摄入含一定量乳糖的牛奶后出现腹部不适症状,主观认为是乳糖不耐受患者,因此避免食用乳制品,这可能会给他们带来长期的健康危害。而目前却缺乏有关人群主观乳糖不耐受的报道以及由此引起的牛奶及奶制品摄入的变化。
目的:了解杭州市区人群中主观乳糖不耐受的发生率,并对其相关因素进行探讨。
方法:按照分层整群随机抽样调查原则,在杭州市抽取3个区,然后在每个区中各抽取一个社区作为调查点,对社区居民进行抽样调查。采用问卷调查的方式,以面对面询问的方式回答问卷。问卷内容包括个人饮用牛奶及奶制品情况(包括种类及量),饮用牛奶及奶制品后是否出现腹部不适症状(包括腹胀、胃肠胀气、腹鸣、腹痛、腹泻、恶心、呕吐等),以及生活事件量表、医院焦虑抑郁量表和肠道症状量表。采用SPSS 13.0统计软件来进行数据的统计分析,Mann-Whitney U test方法用于非正态分布的两组之间的比较,Logistic回归分析用于评价乳糖摄入在性别、年龄段之间有无差异以及主观乳糖不耐受者与乳糖耐受者之间的多因素分析。
结果:本研究共调查了800人,有68人因调查问卷资料填写不完整而剔除出本研究,最后纳入分析的有效调查问卷有732份,男性261例,女性471例,年龄17-75岁,平均46.12±14.77岁。主观乳糖不耐受者135例,男性40例,女性95例,平均年龄45.59±14.60岁,其中轻度腹部不适111例,中度不适16例,重度不适8例。人群中以牛奶消费为主,其次是酸奶及调味奶,而奶粉及炼乳或浓缩乳消费者很少,大多数消费酸奶量多的人群却对牛奶的消费量相对少。人群乳制品消费种类不同的原因中,无饮用乳制品习惯的有413例(56.4%,413/732),有166例认为不喜欢某种(些)乳制品的口味(22.7%),有135例认为自己饮用乳制品后出现腹部症状(18.4%),只有18例(2.5%)认为经济上难以承受对于乳制品的每日消费。乳制品中乳糖的摄入量,女性高于男性,差异有统计学意义,且随着年龄的增长,乳糖摄入量逐渐减少,30岁以下人群和60岁以上人群间乳糖摄入存在显著性差异。主观乳糖不耐受者乳制品及乳糖的摄入量较无症状的人群明显减少,差异有统计学意义。主观乳糖不耐受者与耐受者在性别、年龄、家庭人均月收入、职业及受教育程度等方面无显著性差异。在焦虑评分、抑郁评分、生活应激评分及肠道症状评分方面,主观乳糖不耐受者均高于耐受者,但仅焦虑评分的差异有统计学意义。
结论:杭州市区人群随着年龄的增长,乳制品及乳糖摄入量逐渐减少。人群中主观乳糖不耐受的比率较高,且主观乳糖不耐受者乳制品及乳糖的摄入量较无症状人群明显减少。焦虑状态水平在主观乳糖不耐受者中高于乳糖耐受者。
1.2主观乳糖不耐受和实际乳糖不耐受的相关性的研究
背景:关于乳糖不耐受的研究很多,然而对于乳糖不耐受的误解仍然比较普遍。主观乳糖不耐受人群中部分实际上能正常消化乳糖,因此对主观乳糖不耐受人群的判定很重要。
目的:探讨主观乳糖不耐受与实际乳糖不耐受的情况,评价主观乳糖不耐受与实际乳糖不耐受的相关性。
方法:研究对象为在杭州居住的人群,根据纳入和排除标准最终确定入选的研究对象。对研究对象采用问卷调查的方式,以面对面询问的方式回答问卷。问卷内容包括个人饮用牛奶及奶制品情况(包括种类及量),饮用牛奶及奶制品后是否出现腹部不适症状(包括腹胀、排气增多、腹鸣、腹痛、腹泻、恶心、呕吐等),以及最近三个月内腹痛及大便情况,和生活事件量表、医院焦虑抑郁量表和肠道症状量表。个体饮用牛奶及奶制品后出现腹部不适症状或因上述腹部症状而拒绝饮用者,判定为主观乳糖不耐受。所有研究对象均行乳糖氢呼气试验检查。若氢气浓度升高超过基础值20ppm以上水平并伴有消化道症状或出现消化道症状而不论氢气浓度变化是否超过基础值20ppm,判定为乳糖不耐受;氢气浓度升高超过基础值20ppm以上水平但不伴有消化道症状为乳糖消化不良;氢气浓度变化不超过基础值20ppm水平,且不伴有消化道症状为乳糖正常消化。记录氢呼气试验检查中和检查后12小时内的腹部症状评分,症状评分为摄入乳糖后12h内各症状评分系数与其严重程度乘积之和。采用SPSS 13.0统计软件来进行统计分析。卡方检验用于主观乳糖不耐受与氢呼气试验检测的实际乳糖不耐受之间的比较,Logistic回归分析用于评价主观乳糖不耐受者中三种乳糖消化吸收类型之间的多因素分析。单因素方差分析用于评价乳糖摄入在性别之间有无差异,Mann-Whitney U test方法用于非正态分布的两组之间的比较。
结果:共有209人纳入本研究,且都经历了20g乳糖氢呼气试验检查。209例中,乳糖不耐受者139例(66.5%),男性74例,女性65例;乳糖消化不良37例(17.7%),男性17例,女性20例;乳糖正常消化者33例(15.8%),男性14例,女性19例。三种类型在男女性别方面无统计学差异。本研究中主观乳糖不耐受54例,占本研究对象的25.8%(54/209),其中经乳糖氢呼气试验诊断为乳糖不耐受42例(77.8%,42/54),乳糖消化不良5例(9.2%),乳糖正常消化7例(13.0%)。问卷调查的主观乳糖不耐受对于实际乳糖不耐受判定的敏感度为30.2%(42/139),特异度为82.9%(58/70),阳性预测值为77.8%(42/54),阴性预测值为37.4%(58/155)。54例主观乳糖不耐受者采用ROMEⅢ标准来诊断,有35例为肠易激综合征,其中实际乳糖不耐受29例,乳糖消化不良3例,乳糖正常消化3例。主观乳糖不耐受中的实际乳糖不耐受、乳糖消化不良及乳糖正常吸收与肠易激综合征之间无统计学差异(p=0.394)。主观乳糖不耐受者中三种乳糖消化吸收的类型之间在性别、年龄、家庭人均月收入、职业及受教育程度、焦虑评分、抑郁评分、生活应激评分及肠道症状评分等方面均无统计学差异。
结论:主观乳糖不耐受不能准确地反应中国人群中实际乳糖不耐受情况。主观乳糖不耐受的灵敏度低且特异度不够高,不能很好地判定实际乳糖不耐受,但其有一定的阳性预测值,有助于提高实际乳糖不耐受的检出率。对于主观乳糖不耐受者,应行乳糖氢呼气试验以明确其具体类型并排除被误认为是主观乳糖不耐受的人群。另外,乳糖氢呼气试验能发现一些潜在的乳糖不耐受者。
2乳糖不耐受与乳糖消化不良间差异的机制研究
背景:在乳糖酶缺乏者中,一些人群表现为乳糖消化不良,而另一些人群则表现为乳糖不耐受,且不耐受症状各异,对于乳糖不耐受与乳糖消化不良间差异的机制目前尚未十分明确。
目的:探讨乳糖不耐受与乳糖消化不良在胃肠道动力及肠道菌群间的差异,以及它们之间的相互影响。
方法:对无器质性疾病的成年人,行乳糖氢呼气试验检查及记录腹部症状(腹鸣、腹胀、腹痛及腹泻等),确定其是否为乳糖不耐受、乳糖消化不良或乳糖正常消化。评估乳糖不耐受者的腹部症状评分,并通过氢呼气试验评价口盲肠转运时间。运用荧光原位杂交技术,选择5种特异性的探针检测乳糖不耐受、乳糖消化不良及乳糖正常消化者的肠道菌群情况。
结果:163例研究对象中,男性80例,女性83例,其中乳糖不耐受有117例(男性62例,女性55例),乳糖消化不良24例(男性9例,女性15例),乳糖正常消化22例(男性9例,女性13例)。乳糖不耐受与乳糖消化不良在年龄及性别之间无统计学差异。乳糖不耐受的口盲肠转运时间为54.23±30.12分钟,而乳糖消化不良的口盲肠转运时间为77.50±31.49分钟,两者间差异有统计学意义,且口盲肠转运时间的OR值为0.977,有统计学意义(p=0.003)。运用荧光原位杂交技术,发现肠道总细菌量及4种特异性探针所对应的肠道细菌量在乳糖不耐受、乳糖消化不良及乳糖正常消化三者间存在差异。与Bac303探针杂交的拟杆菌属和普霍沃勒菌属及与Erec482探针杂交的直肠真杆菌-球形梭菌属,在乳糖不耐受者中明显高于乳糖消化不良和乳糖正常消化者;而与Bif164杂交的双歧杆菌属及与Lab722杂交的乳杆菌属,在乳糖不耐受者中明显低于乳糖消化不良和乳糖正常消化者,p值均<0.05,差异有统计学意义。
结论:口盲肠转运时间和肠道菌群组成变化与乳糖不耐受密切相关。乳糖不耐受者的口盲肠转运时间较乳糖消化不良者明显缩短。乳糖不耐受、乳糖消化不良及乳糖正常消化三者间的肠道菌群组成存在显著差异。乳糖不耐受者的肠道拟杆菌属和普霍沃勒菌属及直肠真杆菌-球形梭菌属明显高于乳糖消化不良和乳糖正常消化者,而双歧杆菌属及乳杆菌属明显低于乳糖消化不良和乳糖正常消化者。
3杭州市区人群乳糖酶基因多态性与乳糖酶持续的相关性的研究
背景:乳糖酶持续的频率在不同人群中存在很大的差异,乳糖酶基因的T-13910位点在欧洲人群中与乳糖酶持续密切相关,然而其在非洲人群和中国北部人群并无明显的相关性。
目的:探讨杭州市区人群中乳糖酶基因T-13910等位基因位点情况,以及邻近基因的单核苷酸多态性与乳糖酶持续的相关性。
方法:对无器质性疾病的杭州市区成年人,行乳糖氢呼气试验检查,确定其是否为乳糖酶持续或乳糖酶不持续,并抽取外周血行全血DNA提取,进行PCR扩增及测序,将DNA测序结果进行比对分析以明确T-13910等位基因位点情况,并发现有无新的基因多态性位点。然后将乳糖酶基因型与乳糖酶表现型进行比较及相关性分析。
结果:有163例纳入研究,其中男性80例,女性83例,年龄21-70岁,平均年龄42.20±11.45岁。经乳糖氢呼气试验确定为乳糖酶持续型22例(13.5%,22/163),男性9例,女性13例;另141例为乳糖酶不持续型(86.5%,141/163),男性71例,女性70例。在141例乳糖酶不持续型中,乳糖不耐受117例(83.0%),乳糖消化不良24例(17.0%)。乳糖酶持续与乳糖酶不持续在男女性别方面无统计学差异。在所有被研究人群中均未检测到T-13910基因多态性位点,均为纯合子C/C-13910。也发现人群中存在多个不同于C/T-13910的新的单核苷酸多态性位点,它们分别为C/T-13908、A/C-13926、G/A-14010、T/G-13951、C/T-13952,其中A/C-13926出现在3例不同的DNA序列中,在2例不同的DNA序列中发现C/T-13908多态性位点,G/A-14010单核苷酸多态性位点存在于1例中,而T/G-13951及C/T-13952多态性位点存在于同一例DNA序列中。T-13908等位基因均存在于乳糖酶持续中;C-13926等位基因均存在于乳糖酶不持续中,且T-13908等位基因与乳糖酶持续相关,有统计学意义(p=0.017)。而C-13926等位基因与乳糖酶不持续的相关性无统计学意义。另外,A-14010、G-13951、T-13952等位基因多态性位点与乳糖酶表现型的相关性亦无统计学意义。
结论:首次发现乳糖酶基因在杭州市区人群中有多个新的单核苷酸多态性位点,包括T-13908、C-13926、A-14010、G-13951、T-13952等位基因。T-13908等位基因可能与杭州市区人群的乳糖酶持续相关。乳糖酶持续在杭州市区人群比较少见,乳糖酶基因上游的T-13910等位基因位点的频率很低。T-13910等位基因位点检测法在杭州市区人群中不能预测乳糖酶持续。
1.The epidemiological investigation of subjective lactose intolerance in Hangzhou urban populations
1.1 Investigation of incidence and analysis of relevant factors of lactose intolerance in Hangzhou urban population
Background:Because of lactase deficiency,a lot of people had the symptoms of abdominal discomfort after intaking milk with a certain amount of lactose,and they subjectively thought that they were lactose intolerance,so they avoided eating dairy products,which might give them a long-term health hazards.However,at present,there is a lack of reports about subjective lactose intolerance and the changes on intaking milk and dairy products induced by subjective lactose intolerance.
Aims:To investigate the incidence of subjective lactose intolerance in Hangzhou urban populations,and to explore the related factors.
Methods:In accordance with the stratified group random sampling principle,three districts of Hangzhou Urban were taken in,and then a community was extracted from every district as the points to investigate community residents for sample survey.The questionnaire survey was used by face-to-face inquiry questionnaire approach.The contents of questionnaire included the conditions of personal drinking milk and dairy products(involving the category and quantity) and the symptoms of abdominal discomfort after drinking milk and dairy products(including abdominal distension, gastrointestinal flatulence,borborygmus,abdominal pain,diarrhea,nausea,vomiting, etc.),and included the Life Events Scale,Hospital Anxiety and Depression Scale and Intestinal Symptoms Scale.SPSS 13.0 statistical software was used to conduct statistical analysis.Mann-Whitney U test was used to analyze the non-normal distribution data,and Logistic regression analysis was used to evaluate the differences of lactose intake in gender and age group and multiple factors between subjective lactose intolerance and lactose tolerance.
Results:Eight hundred people were investigated,then 68 people were removed out of this study because of incomplete information in the questionnaire,and finally there were 732 effective questionnaires analyzed.Among them,261 cases were male and 471 cases were female,whose age was 17-75 years old with the average age of 46.12±14.77.In 732 cases,there were 135 cases with subjective lactose intolerance.There were 40 males and 95 females,and the average of age was 45.59±14.60.Among them,111 cases had mild abdominal discomfort,16 cases with moderate and 8 cases with severe discomfort.There was difference in the category of dairy products consumption,and milk consumption was the major,followed by yogurt and flavoring milk.However, there was little consumption in milk powder and condensed milk or concentrated milk. The major population who consumed much yogurt had relative less milk consumption. Among the different reasons about the category of dairy products consumption,there were 413 cases with the non-drinking habits of dairy products(56.4%,413/732);and 166 cases were the cause of disliking dairy taste(22.7%),and 135 cases had abdominal symptoms after dairy products consumption(18.4%),and only 18 cases(2.5%) consider that they could not bear the economy on the daily consumption of dairy products.The intake of lactose from dairy products in women was more than in men,and there was statistical difference.The intake of lactose was gradually reduced with age,and there was significant difference between the people below 30 years of age and people over the age of 60.The intake of dairy products and lactose in subjective lactose intolerance was much less than in asymptomatic population,and there was statistical difference.There were no significant differences between subjective lactose intolerance and lactose tolerance in gender,age,family per capita monthly income,occupation and level of education.The scores of anxiety,depression,life stress and bowel symptoms all were higher in subjective lactose intolerance than in lactose tolerance.However,there was statistical difference only in anxiety.
Conclusions:The intake of dairy products and lactose was gradually reduced with age in Hangzhou urban populations.Among the populations,the ratio of subjective lactose intolerance was high,and the intake of dairy products and lactose in subjective lactose intolerance was much less than in asymptomatic populations.The level of anxiety status was higher in subjective lactose intolerance than in tolerance.
1.2 Research of relevance of subjective lactose intolerance and actual lactose intolerance
Background:There were many researches about lactose intolerance.However,it was still common for misunderstanding in lactose intolerance.In fact,part of people with subjective lactose intolerance could normally digest lactose.Therefore,it was very important on the determination for subjective lactose intolerance.
Aims:To explore the situation of subjective lactose intolerance and actual lactose intolerance,and to evaluate the relevance of subjective lactose intolerance and actual lactose intolerance.
Methods:Study subjects were the people who lived in Hangzhou,and were selected according to the inclusion and exclusion criteria of this study.The questionnaire survey was used by face-to-face inquiry questionnaire approach for subjects.The contents of questionnaire included the conditions of personal drinking milk and dairy products (involving the category and quantity) and the symptoms of abdominal discomfort after drinking milk and dairy products(including abdominal distension,gastrointestinal flatulence,borborygmus,abdominal pain,diarrhea,nausea,vomiting,etc.),and the situation of abdominal pain and stool within nearly three months,and included the Life Events Scale,Hospital Anxiety and Depression Scale and Intestinal Symptoms Scale.If the individual suffered from abdominal discomfort after intaking milk and dairy products,or refused to intake due to the above symptoms of abdominal symptoms,he or she was determined as subjective lactose intolerance.All subjects underwent lactose hydrogen breath test.If the concentration of hydrogen increased over 20ppm of basic values accompanied by gastrointestinal symptoms,or gastrointestinal symptoms were appeared regardless of whether the concentration of hydrogen increased over 20ppm of basic values,it was judged to be lactose intolerance.Lactose maldigestion was judged when the concentration of hydrogen increased over 20ppm of basic values but not accompanied by gastrointestinal symptoms.Lactose normal digestion was defined when the change of hydrogen concentration did not exceed 20ppm of basic values and without gastrointestinal symptoms.The abdominal symptom score,which was the sum of multiplication product of each symptom score coefficient and the degree of severity within 12h after intake of lactose,was recorded during hydrogen breath test and 12 hours later of the test.SPSS 13.0 statistical software was used to conduct statistical analysis.Chi-square test was used for the comparison between subjective lactose intolerance and actual lactose intolerance tested by hydrogen breath test.Logistic regression analysis was used to evaluate the differences of multiple factors among lactose intolerance,lactose maldigestion and digester of subjective lactose intolerance. One-way ANOVA was used to evaluate the difference of lactose intake in gender. Mann-Whitney U test was used to analyze the non-normal distribution data.
Results:A total of 209 people who all had gone through 20g lactose hydrogen breath test were included in this study.Among them,33 cases were lactose normal digestion (15.8%),and there were 14 males and 19 females.37 cases were lactose maldigestion (17.7%,17 males and 20 females),and 139 cases were lactose intolerance(66.5%,74 males and 65 females).There was no statistical difference in three types at gender.In this study,54 cases were subjective lactose intolerance,and the ratio in all subjects was 25.8%(54/209).Among them,there were 42 cases diagnosed as lactose intolerance by lactose hydrogen breath test,and the ratio in subjective lactose intolerance was 77.8% (42/54).There were 5 cases of lactose maldigestion(9.2%) and 7 cases of lactose normal digestion(13.0%).For determining actual lactose intolerance by subjective lactose intolerance from questionnaire,the sensitivity was 30.2%(42/139),the specificity was 82.9%(58/70),the positive predictive value was 77.8%(42/54),and the negative predictive value was 37.4%(58/155).According to the ROMEⅢcriteria, there were 35 cases of irritable bowel syndrome in 54 cases of subjective lactose intolerance.Among the irritable bowel syndrome,29 cases were actual lactose intolerance,three cases were lactose maldigestion and three cases were lactose normal digestion.There was no statistical difference among actual lactose intolerance,lactose maldigestion,lactose normal digestion in subjective lactose intolerance and irritable bowel syndrome(p= 0.394).There were no significant differences among lactose intolerance,lactose maldigestion and digester of subjective lactose intolerance in gender, age,family per capita monthly income,occupation,level of education,anxiety, depression,life stress and bowel symptoms.
Conclusions:Subjective lactose intolerance should not accurately reflect the situation of actual lactose intolerance in Chinese populations.Because the sensitivity was low and the specificity was not enough high,subjective lactose intolerance could not well determine the actual lactose intolerance.However,because of the positive predictive value in a certain degree,it could conduce to improve the detective rate of actual lactose intolerance.Subjective lactose intolerance should be performed lactose hydrogen breath test to clear his or her specific types and exclude the people mistaken for lactose intolerance.In addition,lactose hydrogen breath test was able to detect some potential lactose intolerance.
2 Research of the mechanisms of difference between lactose intolerance and lactose maldigestion
Background:In lactase deficiency,some were lactose maldigestion and others were lactose intolerance,and the symptoms of intolerance were different.There was not yet very clear on the mechanism of difference between lactose intolerance and lactose maldigestion.
Aim:To explore the differences in the gastrointestinal dynamic and intestinal flora between lactose intolerance and lactose maldigestion and the mutual influence between them.
Methods:Lactose hydrogen breath test was done for the adults without organic disease, by which lactose intolerance,lactose maldigestion or lactose normal digestion was identified,and the abdominal symptoms were recorded including borborygmus, abdominal distension,abdominal pain and diarrhea,etc.The abdominal symptom score of lactose intolerance was assessed,and the oral cecum transit time was evaluated by hydrogen breath test.Five kinds of specific probes were selected to detect the intestinal flora of lactose intolerance,lactose maldigestion and lactose normal digestion by fluorescence in situ hybridization.
Results:163 participants were recruited including 80 men and 83 women.Among them, there were 11.7 cases of lactose intolerance(62 males and 55 females),24 cases of lactose maldigestion(9 males,15 females),22 cases of lactose normal digestion,(9 males,13 females).There was no statistical difference between lactose intolerance and lactose maldigestion in age and gender.The oral cecum transit time of lactose intolerance was 54.23±30.12 minutes,while it was 77.50±31.49 minutes for lactose malndigestion,and there was statistical difference between them.The value of OR of the OCTT was 0.977,and there was statistical difference(p=0.003).The total intestinal bacteria and four kinds of intestinal bacteria corresponding to the specific probes were found in the lactose intolerance,lactose maldigestion and lactose normal digestion by fluorescence in situ hybridization,and there were statistical differences among the three types.Bacteroides and Prevolla spp.was specifically hybridized with Bac303 probe and Eubacterium rectale- Clostridium coccoides was specifically hybridized with Erec482 probe.They were significantly higher in lactose intolerance than in lactose maldigestion and lactose normal digestion.Bifidobacterium was specifically hybridized with Bif164 probe and lactobacillus was specifically hybridized with Lab722 probe.They were significantly lower in lactose intolerance than in lactose maldigestion and lactose normal digestion.There were statistical differences(p< 0.05).
Conclusions:It was strong relevance between the oral cecum transit time,the changes of the composition of intestinal flora and lactose intolerance.The oral cecum transit time of lactose intolerance was significantly shorter than of lactose maldigestion.There were significant differences in the composition of the intestinal flora between lactose intolerance,lactose maldigestion and lactose normal digestion.It was significantly higher for Bacteroides and Prevolla spp.and Eubacterium rectale- Clostridium coccoides in lactose intolerance than in lactose maldigestion and lactose normal digestion,while Bifidobacterium and Lactobacillus were significantly lower in lactose intolerance than in lactose maldigestion and lactose normal digestion.
3 Research of correlation between lactase gene polymorphisms and lactase persistence in Hangzhou urban populations
Background:The frequency of lactase persistence varies widely in different human populations.A single nucleotide polymorphism in the gene encoding lactase(T-13910) is associated with the ability to digest milk as adults(lactase persistence) in Europeans, but it is not associated in Africans and north China.
Aim:To explore the situation of T-13910 lactase gene polymorphism,and to evaluate the correlation between the lactase genetic polymorphisms and lactase persistence in Hangzhou urban populations.
Methods:Lactose hydrogen breath test was done for the adults in Hangzhou urban populations without organic disease,by which lactase persistence or lactase non-persistence was identified.DNA was extracted from peripheral blood,and then the Polymerase Chain Reaction and sequencing was done.The outcome of the DNA sequencing was blasted in GenBank to find whether there were new polymorphisms of lactase gene.Lactase genotype and lactase phenotype were compared and analyzed.
Results:One hundred and sixty-three participants from the Hangzhou urban populations were recruited.Among them,there were eighty men and eighty-three women.Their age was from 21 to 70 years,and the average age was 42.20±11.45 years.In these 163 participants,lactase persistence was found in 22 cases(22/163, 13.5%,9 males,13 females),and lactase non-persistence was 141 cases(141/163, 86.5%,71 males,70 females) by lactose hydrogen breath test.Among lactase non-persistence,lactose intolerance was 117 cases(117/141,83.0%) and lactose maldigestion was 24 cases(24/141,17.0%).There was no statistical difference in gender between lactase persistence and lactase non-persistence.The frequency of lactase persistence was very low in Hangzhou urban populations.T-13910 allele was not detected in all cases,in turn,the homozygote C/C-13910 was found in this location. Several other new polymorphisms sites different from C/T-13910 were found,such as C/T-13908,A/C-13926,G/A-14010,T/G-13951 and C/T-13952.Among these polymorphisms sites,A/C-13926 was found in three different cases,C/T-13908 in two, G/A-14010 in one,T/G-13951and C/T-13952 in the same case.The T-13908 allele all existed in lactase persistence,and the C-13926 allele all existed in lactase non-persistence.The T-13908 allele was associated with lactase persistence,and there was statistical difference(p= 0.017).However,there was no statistical difference between C-13926 allele and the correlation of lactase non-persistence.In addition,there was no statistical difference between A-14010,G-13951,T-13952 allele and lactase phenotype.
Conclusions:It was first report that there were many new single nucleotide polymorphisms of lactase gene in this study including T-13908、C-13926、A-14010、G-13951、T-13952 allele,and T-13908 allele might be associated with lactase persistence in Hangzhou urban populations.The frequency of lactase persistence was very rare in Hangzhou urban populations.The T-13910 allele frequency was very low and it did not match the lactase persistence phenotype in these populations.Therefore the T-13910 allele could not be served as a predictor for lactase persistence in Hangzhou urban populations.
1.1杭州市区人群乳糖不耐受发生率调查及相关因素分析
背景:由于乳糖酶的缺乏,很多人群摄入含一定量乳糖的牛奶后出现腹部不适症状,主观认为是乳糖不耐受患者,因此避免食用乳制品,这可能会给他们带来长期的健康危害。而目前却缺乏有关人群主观乳糖不耐受的报道以及由此引起的牛奶及奶制品摄入的变化。
目的:了解杭州市区人群中主观乳糖不耐受的发生率,并对其相关因素进行探讨。
方法:按照分层整群随机抽样调查原则,在杭州市抽取3个区,然后在每个区中各抽取一个社区作为调查点,对社区居民进行抽样调查。采用问卷调查的方式,以面对面询问的方式回答问卷。问卷内容包括个人饮用牛奶及奶制品情况(包括种类及量),饮用牛奶及奶制品后是否出现腹部不适症状(包括腹胀、胃肠胀气、腹鸣、腹痛、腹泻、恶心、呕吐等),以及生活事件量表、医院焦虑抑郁量表和肠道症状量表。采用SPSS 13.0统计软件来进行数据的统计分析,Mann-Whitney U test方法用于非正态分布的两组之间的比较,Logistic回归分析用于评价乳糖摄入在性别、年龄段之间有无差异以及主观乳糖不耐受者与乳糖耐受者之间的多因素分析。
结果:本研究共调查了800人,有68人因调查问卷资料填写不完整而剔除出本研究,最后纳入分析的有效调查问卷有732份,男性261例,女性471例,年龄17-75岁,平均46.12±14.77岁。主观乳糖不耐受者135例,男性40例,女性95例,平均年龄45.59±14.60岁,其中轻度腹部不适111例,中度不适16例,重度不适8例。人群中以牛奶消费为主,其次是酸奶及调味奶,而奶粉及炼乳或浓缩乳消费者很少,大多数消费酸奶量多的人群却对牛奶的消费量相对少。人群乳制品消费种类不同的原因中,无饮用乳制品习惯的有413例(56.4%,413/732),有166例认为不喜欢某种(些)乳制品的口味(22.7%),有135例认为自己饮用乳制品后出现腹部症状(18.4%),只有18例(2.5%)认为经济上难以承受对于乳制品的每日消费。乳制品中乳糖的摄入量,女性高于男性,差异有统计学意义,且随着年龄的增长,乳糖摄入量逐渐减少,30岁以下人群和60岁以上人群间乳糖摄入存在显著性差异。主观乳糖不耐受者乳制品及乳糖的摄入量较无症状的人群明显减少,差异有统计学意义。主观乳糖不耐受者与耐受者在性别、年龄、家庭人均月收入、职业及受教育程度等方面无显著性差异。在焦虑评分、抑郁评分、生活应激评分及肠道症状评分方面,主观乳糖不耐受者均高于耐受者,但仅焦虑评分的差异有统计学意义。
结论:杭州市区人群随着年龄的增长,乳制品及乳糖摄入量逐渐减少。人群中主观乳糖不耐受的比率较高,且主观乳糖不耐受者乳制品及乳糖的摄入量较无症状人群明显减少。焦虑状态水平在主观乳糖不耐受者中高于乳糖耐受者。
1.2主观乳糖不耐受和实际乳糖不耐受的相关性的研究
背景:关于乳糖不耐受的研究很多,然而对于乳糖不耐受的误解仍然比较普遍。主观乳糖不耐受人群中部分实际上能正常消化乳糖,因此对主观乳糖不耐受人群的判定很重要。
目的:探讨主观乳糖不耐受与实际乳糖不耐受的情况,评价主观乳糖不耐受与实际乳糖不耐受的相关性。
方法:研究对象为在杭州居住的人群,根据纳入和排除标准最终确定入选的研究对象。对研究对象采用问卷调查的方式,以面对面询问的方式回答问卷。问卷内容包括个人饮用牛奶及奶制品情况(包括种类及量),饮用牛奶及奶制品后是否出现腹部不适症状(包括腹胀、排气增多、腹鸣、腹痛、腹泻、恶心、呕吐等),以及最近三个月内腹痛及大便情况,和生活事件量表、医院焦虑抑郁量表和肠道症状量表。个体饮用牛奶及奶制品后出现腹部不适症状或因上述腹部症状而拒绝饮用者,判定为主观乳糖不耐受。所有研究对象均行乳糖氢呼气试验检查。若氢气浓度升高超过基础值20ppm以上水平并伴有消化道症状或出现消化道症状而不论氢气浓度变化是否超过基础值20ppm,判定为乳糖不耐受;氢气浓度升高超过基础值20ppm以上水平但不伴有消化道症状为乳糖消化不良;氢气浓度变化不超过基础值20ppm水平,且不伴有消化道症状为乳糖正常消化。记录氢呼气试验检查中和检查后12小时内的腹部症状评分,症状评分为摄入乳糖后12h内各症状评分系数与其严重程度乘积之和。采用SPSS 13.0统计软件来进行统计分析。卡方检验用于主观乳糖不耐受与氢呼气试验检测的实际乳糖不耐受之间的比较,Logistic回归分析用于评价主观乳糖不耐受者中三种乳糖消化吸收类型之间的多因素分析。单因素方差分析用于评价乳糖摄入在性别之间有无差异,Mann-Whitney U test方法用于非正态分布的两组之间的比较。
结果:共有209人纳入本研究,且都经历了20g乳糖氢呼气试验检查。209例中,乳糖不耐受者139例(66.5%),男性74例,女性65例;乳糖消化不良37例(17.7%),男性17例,女性20例;乳糖正常消化者33例(15.8%),男性14例,女性19例。三种类型在男女性别方面无统计学差异。本研究中主观乳糖不耐受54例,占本研究对象的25.8%(54/209),其中经乳糖氢呼气试验诊断为乳糖不耐受42例(77.8%,42/54),乳糖消化不良5例(9.2%),乳糖正常消化7例(13.0%)。问卷调查的主观乳糖不耐受对于实际乳糖不耐受判定的敏感度为30.2%(42/139),特异度为82.9%(58/70),阳性预测值为77.8%(42/54),阴性预测值为37.4%(58/155)。54例主观乳糖不耐受者采用ROMEⅢ标准来诊断,有35例为肠易激综合征,其中实际乳糖不耐受29例,乳糖消化不良3例,乳糖正常消化3例。主观乳糖不耐受中的实际乳糖不耐受、乳糖消化不良及乳糖正常吸收与肠易激综合征之间无统计学差异(p=0.394)。主观乳糖不耐受者中三种乳糖消化吸收的类型之间在性别、年龄、家庭人均月收入、职业及受教育程度、焦虑评分、抑郁评分、生活应激评分及肠道症状评分等方面均无统计学差异。
结论:主观乳糖不耐受不能准确地反应中国人群中实际乳糖不耐受情况。主观乳糖不耐受的灵敏度低且特异度不够高,不能很好地判定实际乳糖不耐受,但其有一定的阳性预测值,有助于提高实际乳糖不耐受的检出率。对于主观乳糖不耐受者,应行乳糖氢呼气试验以明确其具体类型并排除被误认为是主观乳糖不耐受的人群。另外,乳糖氢呼气试验能发现一些潜在的乳糖不耐受者。
2乳糖不耐受与乳糖消化不良间差异的机制研究
背景:在乳糖酶缺乏者中,一些人群表现为乳糖消化不良,而另一些人群则表现为乳糖不耐受,且不耐受症状各异,对于乳糖不耐受与乳糖消化不良间差异的机制目前尚未十分明确。
目的:探讨乳糖不耐受与乳糖消化不良在胃肠道动力及肠道菌群间的差异,以及它们之间的相互影响。
方法:对无器质性疾病的成年人,行乳糖氢呼气试验检查及记录腹部症状(腹鸣、腹胀、腹痛及腹泻等),确定其是否为乳糖不耐受、乳糖消化不良或乳糖正常消化。评估乳糖不耐受者的腹部症状评分,并通过氢呼气试验评价口盲肠转运时间。运用荧光原位杂交技术,选择5种特异性的探针检测乳糖不耐受、乳糖消化不良及乳糖正常消化者的肠道菌群情况。
结果:163例研究对象中,男性80例,女性83例,其中乳糖不耐受有117例(男性62例,女性55例),乳糖消化不良24例(男性9例,女性15例),乳糖正常消化22例(男性9例,女性13例)。乳糖不耐受与乳糖消化不良在年龄及性别之间无统计学差异。乳糖不耐受的口盲肠转运时间为54.23±30.12分钟,而乳糖消化不良的口盲肠转运时间为77.50±31.49分钟,两者间差异有统计学意义,且口盲肠转运时间的OR值为0.977,有统计学意义(p=0.003)。运用荧光原位杂交技术,发现肠道总细菌量及4种特异性探针所对应的肠道细菌量在乳糖不耐受、乳糖消化不良及乳糖正常消化三者间存在差异。与Bac303探针杂交的拟杆菌属和普霍沃勒菌属及与Erec482探针杂交的直肠真杆菌-球形梭菌属,在乳糖不耐受者中明显高于乳糖消化不良和乳糖正常消化者;而与Bif164杂交的双歧杆菌属及与Lab722杂交的乳杆菌属,在乳糖不耐受者中明显低于乳糖消化不良和乳糖正常消化者,p值均<0.05,差异有统计学意义。
结论:口盲肠转运时间和肠道菌群组成变化与乳糖不耐受密切相关。乳糖不耐受者的口盲肠转运时间较乳糖消化不良者明显缩短。乳糖不耐受、乳糖消化不良及乳糖正常消化三者间的肠道菌群组成存在显著差异。乳糖不耐受者的肠道拟杆菌属和普霍沃勒菌属及直肠真杆菌-球形梭菌属明显高于乳糖消化不良和乳糖正常消化者,而双歧杆菌属及乳杆菌属明显低于乳糖消化不良和乳糖正常消化者。
3杭州市区人群乳糖酶基因多态性与乳糖酶持续的相关性的研究
背景:乳糖酶持续的频率在不同人群中存在很大的差异,乳糖酶基因的T-13910位点在欧洲人群中与乳糖酶持续密切相关,然而其在非洲人群和中国北部人群并无明显的相关性。
目的:探讨杭州市区人群中乳糖酶基因T-13910等位基因位点情况,以及邻近基因的单核苷酸多态性与乳糖酶持续的相关性。
方法:对无器质性疾病的杭州市区成年人,行乳糖氢呼气试验检查,确定其是否为乳糖酶持续或乳糖酶不持续,并抽取外周血行全血DNA提取,进行PCR扩增及测序,将DNA测序结果进行比对分析以明确T-13910等位基因位点情况,并发现有无新的基因多态性位点。然后将乳糖酶基因型与乳糖酶表现型进行比较及相关性分析。
结果:有163例纳入研究,其中男性80例,女性83例,年龄21-70岁,平均年龄42.20±11.45岁。经乳糖氢呼气试验确定为乳糖酶持续型22例(13.5%,22/163),男性9例,女性13例;另141例为乳糖酶不持续型(86.5%,141/163),男性71例,女性70例。在141例乳糖酶不持续型中,乳糖不耐受117例(83.0%),乳糖消化不良24例(17.0%)。乳糖酶持续与乳糖酶不持续在男女性别方面无统计学差异。在所有被研究人群中均未检测到T-13910基因多态性位点,均为纯合子C/C-13910。也发现人群中存在多个不同于C/T-13910的新的单核苷酸多态性位点,它们分别为C/T-13908、A/C-13926、G/A-14010、T/G-13951、C/T-13952,其中A/C-13926出现在3例不同的DNA序列中,在2例不同的DNA序列中发现C/T-13908多态性位点,G/A-14010单核苷酸多态性位点存在于1例中,而T/G-13951及C/T-13952多态性位点存在于同一例DNA序列中。T-13908等位基因均存在于乳糖酶持续中;C-13926等位基因均存在于乳糖酶不持续中,且T-13908等位基因与乳糖酶持续相关,有统计学意义(p=0.017)。而C-13926等位基因与乳糖酶不持续的相关性无统计学意义。另外,A-14010、G-13951、T-13952等位基因多态性位点与乳糖酶表现型的相关性亦无统计学意义。
结论:首次发现乳糖酶基因在杭州市区人群中有多个新的单核苷酸多态性位点,包括T-13908、C-13926、A-14010、G-13951、T-13952等位基因。T-13908等位基因可能与杭州市区人群的乳糖酶持续相关。乳糖酶持续在杭州市区人群比较少见,乳糖酶基因上游的T-13910等位基因位点的频率很低。T-13910等位基因位点检测法在杭州市区人群中不能预测乳糖酶持续。
1.The epidemiological investigation of subjective lactose intolerance in Hangzhou urban populations
1.1 Investigation of incidence and analysis of relevant factors of lactose intolerance in Hangzhou urban population
Background:Because of lactase deficiency,a lot of people had the symptoms of abdominal discomfort after intaking milk with a certain amount of lactose,and they subjectively thought that they were lactose intolerance,so they avoided eating dairy products,which might give them a long-term health hazards.However,at present,there is a lack of reports about subjective lactose intolerance and the changes on intaking milk and dairy products induced by subjective lactose intolerance.
Aims:To investigate the incidence of subjective lactose intolerance in Hangzhou urban populations,and to explore the related factors.
Methods:In accordance with the stratified group random sampling principle,three districts of Hangzhou Urban were taken in,and then a community was extracted from every district as the points to investigate community residents for sample survey.The questionnaire survey was used by face-to-face inquiry questionnaire approach.The contents of questionnaire included the conditions of personal drinking milk and dairy products(involving the category and quantity) and the symptoms of abdominal discomfort after drinking milk and dairy products(including abdominal distension, gastrointestinal flatulence,borborygmus,abdominal pain,diarrhea,nausea,vomiting, etc.),and included the Life Events Scale,Hospital Anxiety and Depression Scale and Intestinal Symptoms Scale.SPSS 13.0 statistical software was used to conduct statistical analysis.Mann-Whitney U test was used to analyze the non-normal distribution data,and Logistic regression analysis was used to evaluate the differences of lactose intake in gender and age group and multiple factors between subjective lactose intolerance and lactose tolerance.
Results:Eight hundred people were investigated,then 68 people were removed out of this study because of incomplete information in the questionnaire,and finally there were 732 effective questionnaires analyzed.Among them,261 cases were male and 471 cases were female,whose age was 17-75 years old with the average age of 46.12±14.77.In 732 cases,there were 135 cases with subjective lactose intolerance.There were 40 males and 95 females,and the average of age was 45.59±14.60.Among them,111 cases had mild abdominal discomfort,16 cases with moderate and 8 cases with severe discomfort.There was difference in the category of dairy products consumption,and milk consumption was the major,followed by yogurt and flavoring milk.However, there was little consumption in milk powder and condensed milk or concentrated milk. The major population who consumed much yogurt had relative less milk consumption. Among the different reasons about the category of dairy products consumption,there were 413 cases with the non-drinking habits of dairy products(56.4%,413/732);and 166 cases were the cause of disliking dairy taste(22.7%),and 135 cases had abdominal symptoms after dairy products consumption(18.4%),and only 18 cases(2.5%) consider that they could not bear the economy on the daily consumption of dairy products.The intake of lactose from dairy products in women was more than in men,and there was statistical difference.The intake of lactose was gradually reduced with age,and there was significant difference between the people below 30 years of age and people over the age of 60.The intake of dairy products and lactose in subjective lactose intolerance was much less than in asymptomatic population,and there was statistical difference.There were no significant differences between subjective lactose intolerance and lactose tolerance in gender,age,family per capita monthly income,occupation and level of education.The scores of anxiety,depression,life stress and bowel symptoms all were higher in subjective lactose intolerance than in lactose tolerance.However,there was statistical difference only in anxiety.
Conclusions:The intake of dairy products and lactose was gradually reduced with age in Hangzhou urban populations.Among the populations,the ratio of subjective lactose intolerance was high,and the intake of dairy products and lactose in subjective lactose intolerance was much less than in asymptomatic populations.The level of anxiety status was higher in subjective lactose intolerance than in tolerance.
1.2 Research of relevance of subjective lactose intolerance and actual lactose intolerance
Background:There were many researches about lactose intolerance.However,it was still common for misunderstanding in lactose intolerance.In fact,part of people with subjective lactose intolerance could normally digest lactose.Therefore,it was very important on the determination for subjective lactose intolerance.
Aims:To explore the situation of subjective lactose intolerance and actual lactose intolerance,and to evaluate the relevance of subjective lactose intolerance and actual lactose intolerance.
Methods:Study subjects were the people who lived in Hangzhou,and were selected according to the inclusion and exclusion criteria of this study.The questionnaire survey was used by face-to-face inquiry questionnaire approach for subjects.The contents of questionnaire included the conditions of personal drinking milk and dairy products (involving the category and quantity) and the symptoms of abdominal discomfort after drinking milk and dairy products(including abdominal distension,gastrointestinal flatulence,borborygmus,abdominal pain,diarrhea,nausea,vomiting,etc.),and the situation of abdominal pain and stool within nearly three months,and included the Life Events Scale,Hospital Anxiety and Depression Scale and Intestinal Symptoms Scale.If the individual suffered from abdominal discomfort after intaking milk and dairy products,or refused to intake due to the above symptoms of abdominal symptoms,he or she was determined as subjective lactose intolerance.All subjects underwent lactose hydrogen breath test.If the concentration of hydrogen increased over 20ppm of basic values accompanied by gastrointestinal symptoms,or gastrointestinal symptoms were appeared regardless of whether the concentration of hydrogen increased over 20ppm of basic values,it was judged to be lactose intolerance.Lactose maldigestion was judged when the concentration of hydrogen increased over 20ppm of basic values but not accompanied by gastrointestinal symptoms.Lactose normal digestion was defined when the change of hydrogen concentration did not exceed 20ppm of basic values and without gastrointestinal symptoms.The abdominal symptom score,which was the sum of multiplication product of each symptom score coefficient and the degree of severity within 12h after intake of lactose,was recorded during hydrogen breath test and 12 hours later of the test.SPSS 13.0 statistical software was used to conduct statistical analysis.Chi-square test was used for the comparison between subjective lactose intolerance and actual lactose intolerance tested by hydrogen breath test.Logistic regression analysis was used to evaluate the differences of multiple factors among lactose intolerance,lactose maldigestion and digester of subjective lactose intolerance. One-way ANOVA was used to evaluate the difference of lactose intake in gender. Mann-Whitney U test was used to analyze the non-normal distribution data.
Results:A total of 209 people who all had gone through 20g lactose hydrogen breath test were included in this study.Among them,33 cases were lactose normal digestion (15.8%),and there were 14 males and 19 females.37 cases were lactose maldigestion (17.7%,17 males and 20 females),and 139 cases were lactose intolerance(66.5%,74 males and 65 females).There was no statistical difference in three types at gender.In this study,54 cases were subjective lactose intolerance,and the ratio in all subjects was 25.8%(54/209).Among them,there were 42 cases diagnosed as lactose intolerance by lactose hydrogen breath test,and the ratio in subjective lactose intolerance was 77.8% (42/54).There were 5 cases of lactose maldigestion(9.2%) and 7 cases of lactose normal digestion(13.0%).For determining actual lactose intolerance by subjective lactose intolerance from questionnaire,the sensitivity was 30.2%(42/139),the specificity was 82.9%(58/70),the positive predictive value was 77.8%(42/54),and the negative predictive value was 37.4%(58/155).According to the ROMEⅢcriteria, there were 35 cases of irritable bowel syndrome in 54 cases of subjective lactose intolerance.Among the irritable bowel syndrome,29 cases were actual lactose intolerance,three cases were lactose maldigestion and three cases were lactose normal digestion.There was no statistical difference among actual lactose intolerance,lactose maldigestion,lactose normal digestion in subjective lactose intolerance and irritable bowel syndrome(p= 0.394).There were no significant differences among lactose intolerance,lactose maldigestion and digester of subjective lactose intolerance in gender, age,family per capita monthly income,occupation,level of education,anxiety, depression,life stress and bowel symptoms.
Conclusions:Subjective lactose intolerance should not accurately reflect the situation of actual lactose intolerance in Chinese populations.Because the sensitivity was low and the specificity was not enough high,subjective lactose intolerance could not well determine the actual lactose intolerance.However,because of the positive predictive value in a certain degree,it could conduce to improve the detective rate of actual lactose intolerance.Subjective lactose intolerance should be performed lactose hydrogen breath test to clear his or her specific types and exclude the people mistaken for lactose intolerance.In addition,lactose hydrogen breath test was able to detect some potential lactose intolerance.
2 Research of the mechanisms of difference between lactose intolerance and lactose maldigestion
Background:In lactase deficiency,some were lactose maldigestion and others were lactose intolerance,and the symptoms of intolerance were different.There was not yet very clear on the mechanism of difference between lactose intolerance and lactose maldigestion.
Aim:To explore the differences in the gastrointestinal dynamic and intestinal flora between lactose intolerance and lactose maldigestion and the mutual influence between them.
Methods:Lactose hydrogen breath test was done for the adults without organic disease, by which lactose intolerance,lactose maldigestion or lactose normal digestion was identified,and the abdominal symptoms were recorded including borborygmus, abdominal distension,abdominal pain and diarrhea,etc.The abdominal symptom score of lactose intolerance was assessed,and the oral cecum transit time was evaluated by hydrogen breath test.Five kinds of specific probes were selected to detect the intestinal flora of lactose intolerance,lactose maldigestion and lactose normal digestion by fluorescence in situ hybridization.
Results:163 participants were recruited including 80 men and 83 women.Among them, there were 11.7 cases of lactose intolerance(62 males and 55 females),24 cases of lactose maldigestion(9 males,15 females),22 cases of lactose normal digestion,(9 males,13 females).There was no statistical difference between lactose intolerance and lactose maldigestion in age and gender.The oral cecum transit time of lactose intolerance was 54.23±30.12 minutes,while it was 77.50±31.49 minutes for lactose malndigestion,and there was statistical difference between them.The value of OR of the OCTT was 0.977,and there was statistical difference(p=0.003).The total intestinal bacteria and four kinds of intestinal bacteria corresponding to the specific probes were found in the lactose intolerance,lactose maldigestion and lactose normal digestion by fluorescence in situ hybridization,and there were statistical differences among the three types.Bacteroides and Prevolla spp.was specifically hybridized with Bac303 probe and Eubacterium rectale- Clostridium coccoides was specifically hybridized with Erec482 probe.They were significantly higher in lactose intolerance than in lactose maldigestion and lactose normal digestion.Bifidobacterium was specifically hybridized with Bif164 probe and lactobacillus was specifically hybridized with Lab722 probe.They were significantly lower in lactose intolerance than in lactose maldigestion and lactose normal digestion.There were statistical differences(p< 0.05).
Conclusions:It was strong relevance between the oral cecum transit time,the changes of the composition of intestinal flora and lactose intolerance.The oral cecum transit time of lactose intolerance was significantly shorter than of lactose maldigestion.There were significant differences in the composition of the intestinal flora between lactose intolerance,lactose maldigestion and lactose normal digestion.It was significantly higher for Bacteroides and Prevolla spp.and Eubacterium rectale- Clostridium coccoides in lactose intolerance than in lactose maldigestion and lactose normal digestion,while Bifidobacterium and Lactobacillus were significantly lower in lactose intolerance than in lactose maldigestion and lactose normal digestion.
3 Research of correlation between lactase gene polymorphisms and lactase persistence in Hangzhou urban populations
Background:The frequency of lactase persistence varies widely in different human populations.A single nucleotide polymorphism in the gene encoding lactase(T-13910) is associated with the ability to digest milk as adults(lactase persistence) in Europeans, but it is not associated in Africans and north China.
Aim:To explore the situation of T-13910 lactase gene polymorphism,and to evaluate the correlation between the lactase genetic polymorphisms and lactase persistence in Hangzhou urban populations.
Methods:Lactose hydrogen breath test was done for the adults in Hangzhou urban populations without organic disease,by which lactase persistence or lactase non-persistence was identified.DNA was extracted from peripheral blood,and then the Polymerase Chain Reaction and sequencing was done.The outcome of the DNA sequencing was blasted in GenBank to find whether there were new polymorphisms of lactase gene.Lactase genotype and lactase phenotype were compared and analyzed.
Results:One hundred and sixty-three participants from the Hangzhou urban populations were recruited.Among them,there were eighty men and eighty-three women.Their age was from 21 to 70 years,and the average age was 42.20±11.45 years.In these 163 participants,lactase persistence was found in 22 cases(22/163, 13.5%,9 males,13 females),and lactase non-persistence was 141 cases(141/163, 86.5%,71 males,70 females) by lactose hydrogen breath test.Among lactase non-persistence,lactose intolerance was 117 cases(117/141,83.0%) and lactose maldigestion was 24 cases(24/141,17.0%).There was no statistical difference in gender between lactase persistence and lactase non-persistence.The frequency of lactase persistence was very low in Hangzhou urban populations.T-13910 allele was not detected in all cases,in turn,the homozygote C/C-13910 was found in this location. Several other new polymorphisms sites different from C/T-13910 were found,such as C/T-13908,A/C-13926,G/A-14010,T/G-13951 and C/T-13952.Among these polymorphisms sites,A/C-13926 was found in three different cases,C/T-13908 in two, G/A-14010 in one,T/G-13951and C/T-13952 in the same case.The T-13908 allele all existed in lactase persistence,and the C-13926 allele all existed in lactase non-persistence.The T-13908 allele was associated with lactase persistence,and there was statistical difference(p= 0.017).However,there was no statistical difference between C-13926 allele and the correlation of lactase non-persistence.In addition,there was no statistical difference between A-14010,G-13951,T-13952 allele and lactase phenotype.
Conclusions:It was first report that there were many new single nucleotide polymorphisms of lactase gene in this study including T-13908、C-13926、A-14010、G-13951、T-13952 allele,and T-13908 allele might be associated with lactase persistence in Hangzhou urban populations.The frequency of lactase persistence was very rare in Hangzhou urban populations.The T-13910 allele frequency was very low and it did not match the lactase persistence phenotype in these populations.Therefore the T-13910 allele could not be served as a predictor for lactase persistence in Hangzhou urban populations.
引文
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