摘要
研究背景
多囊卵巢综合征(PCOS)是青春期及育龄妇女最常见的高度异质性、内分泌代谢紊乱性疾病,PCOS的临床表现具有多样性和复杂性的特点。大量研究提示,该种疾病可能是多种环境因素及多个基因异常共同作用的结果。先前,我们采用全基因组关联研究(GWAS)验证了p值小于10-6基因位点与PCOS密切相关,然而p值小于10-6的基因位点仍有待进一步验证,其中包括RAD54B、GREB1内的相关位点。
研究目的
通过分析比较RAD54B基因rs2930961,GREB1基因rs12470971,rs11686574,rs6740248单核苷酸基因多态位点的等位基因频率及基因型频率在PCOS组和对照组中分布的差异,探讨RAD54B、GREB1基因变异与PCOS发病的相关性；同时比较上述基因多态位点不同基因型患者内分泌、代谢特征表型的差别,从而研究RAD54B基因rs2930961,GREB1基因rs11686574、rs12470971、rs6740248不同基因型与PCOS临床表型的相关性,探讨RAD54B、GREB1基因在PCOS疾病发生、发展及其病理生理过程中的作用。
研究方法
依据2003年鹿特丹标准选择PCOS患者1124例,并选择同期就诊的1067名健康妇女作为对照；提取研究对象全血基因组DNA,测定相应激素水平,包括卵泡刺激素(FSH)、黄体生成素(LH)、雄激素(T)和胰岛素(INS)；所有PCOS患者行OGTT试验,稳态模型评估法(HOMA-IR)估计胰岛素抵抗情况；根据所研究基因的序列设计相应引物,应用TaqMan-MGB实时定量PCR检测体系进行基因型分析。
结果
4个SNP位点的等位基因频率和基因型频率在PCOS患者和对照组之间无显著差异；然而,rs2930961的基因频率在高雄激素血症PCOS患者中有显著不同,meta分析亦发现此倾向,但无法在本研究中证实(P=0.052)。
结论
RAD54B和GREB1基因多态性可能与中国汉族人口PCOS无相关性,但RAD54B可能与PCOS的高雄激素血症有关。
研究背景
先前的GWAS研究表明,9q33.3(rs2479106),2p16.3(rs13405728)和2p21(rs13429458)单核苷酸基因多态(SNP)与PCOS有高度相关性,它们与PCOS的远期并发症一子宫内膜癌是否相关,尚无文献报道。
研究目的
探讨PCOS关联SNP rs2479106(基因DENNDIA),rs13405728(基因LHCGR)和rs13429458(基因THADA)与子宫内膜癌的关系。
研究方法
选取病理学诊断为子宫内膜癌的96位中国汉族妇女和192例健康对照人群进行病例对照研究；采用聚合酶链反应(PCR)对SNP rs2479106,rs13405728和rs13429458进行基因分型并直接测序,以二元逻辑回归模型校正体重指数(BMI)和年龄等混杂因素对试验结果的影响。
结果
SNP rs2479106和rs13405728等位基因频率在子宫内膜癌组和对照组之间存在显著性差异(P<0.05),与子宫内膜样腺癌组比较,差别尤为明显(P<0.01)；其中,rs2479106中G等位基因,rs13405728中的A等位基因增加了子宫内膜腺癌的患病风险。
结论
DENNDIA基因SNP rs2479106、LHCGR基因SNP rs13405728与子宫内膜样腺癌相关。
Background
Polycystic ovary syndrome (PCOS) is the most common highly heterogeneous endocrine and metabolic disorders puberty and women of childbearing age. Many researches showed the disease was related with multiple genetic abnormalities and a variety of environmental factors. Previous genome-wide association study (GWAS) verified these p values less than10E-6and found some meaningful loci of strong associations with PCOS. The present study was performed to investigate loci with p values less than10E-5in gene RAD54B and GREB1.
Objective
The purpose of this study was to determine the relationship between SNPs rs2930961(RAD54B), rs12470971, rs11686574, rs6740248(GREB1) and the pathogenesis of PCOS. Moreover, whether the two genes play a role in endocrine and clinical traits in PCOS patients may provide evidence for a better understanding on the development of PCOS.
Methods
Four single nucleotide polymorphisms (SNP) rs2930961(RAD54B) rs12470971, rs11686574, rs6740248(GREB1) were genotyped in1124PCOS patients diagnosed by the Rotterdam PCOS consensus criteria and1067healthy controls from Han Chinese population. DNAs were extracted from the peripheral blood and serum hormone levels were detected including Follicle stimulating hormone(FSH), luteinizing hormone(LH), testosterone(T) and insulin (INS). All PCOS patients underwent a75g oral glucose tolerance test (OGTT). Insulin resistance was estimated by the homeostasis model assessment method(HOMA-IR). The single real--time quantitative PCR was applied for genotyping by TaqMan-MGB probe assay.
Results
Allele and genotype frequencies of these four SNPs were not significantly different in the replication cohort. However, minor allele frequency of rs2930961was significantly different in hyperandrogenism PCOS and there was a tendency for rs2930961(RAD54B) after meta-analysis by combining the results of these two studies (Pmeta=0.052).
Conclusion
RAD54B and GREB1genes polymorphisms may not be associated with PCOS in Han Chinese population. Nevertheless, RAD54B maybe contribute to hyperandrogenism PCOS patients.
Background
Research shows that SNP9p33.3(rs2479106),2p16.3(rs13405728) and2p21(rsl3429458) may have a high degree correlation with the occurrence of PCOS respectively. Whether they are associated with the long-term complication of PCOS, endometrial carcinoma is unknown. Here, we conducted a case-control study comprising96histologically diagnosed incident endometrial cancer cases and192matched non-cancer controls.
Objective
To explore the PCOS related SNP rs2479106(in gene DENND1A), rs13405728(in gene LHCGR) and rsl3429458(in gene THADA) in women with endometrial carcinoma.
Methods
Information on current body weight, height and age, and past marital and fertile history was obtained from a self-administered questionnaire. The effects of BMI change were evaluated using an unconditional logistic regression model adjusted for potential confounders. Polymerase chain reaction (PCR) was used to evaluate SNP rs2479106, rs13405728and rs13429458.
Results
The allele frequencies of SNP rs2479106and rs13405728were significantly different (P<0.05) between endometrial carcinoma group and control group, and the difference was especially significant in the subgroup of endometrioid adenocarcinoma. Genotyping analysis showed that allele G in rs2479106and allele A in rs13405728could confer risk to endomtrioid adenocarcinoma.
Conclusion
Our results suggest that SNP rs13405728and rs2479106may be associated with endometroid carcinoma.
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