血管紧张素转换酶基因插入/缺失多态性与2型糖尿病合并高血压关系的Meta分析
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摘要
目的研究血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与2型糖尿病合并高血压(T2DM+HTN)发生风险的关系。方法全面检索PubMed、万方数据库、中国知网(CNKI)、维普资讯,收集关于ACE基因I/D多态性与T2DM+HTN发生关系的病例—对照研究,采用优势比(OR)和95%可信区间(95%CI)评估关联强度,应用Rev Man5.3软件对纳入的研究进行异质性检验和合并效应分析,漏斗图评估发表性偏倚。结果共纳入9组病例—对照研究,累计T2DM+HTN组患者554例,T2DM未合并HTN对照组664例。Meta分析结果显示:ACE基因纯合子模型(DD VS Ⅱ)、杂合子模型(ID VS Ⅱ)、显性模型(DD+ID VS Ⅱ)、隐性模型(DD VS Ⅱ+ID)和D等位基因与T2DM+HTN关系的合并OR(95%CI)分别为1.77(1.28～2.45)、1.19(0.90～1.57)、1.28(0.84～1.94)、1.55(0.97～2.46)和1.36(1.04～1.78),对应P值分别为<0.01、0.22、0.25、0.07和0.02。结论 ACE基因I/D多态性可能与T2DM+HTN发病相关。
Objective To evaluate the relationship between angiotensin converting enzyme (ACE)insertion/deletion (I/D) polymorphisms and the risk of type 2 diabetes mellitus combined with hypertension (T2DM+ HTN). Methods Relevant literatures were extensively searched by using PubMed,Wanfang Databases,CNKI and VIP for collecting the case-control studies investigating the relationship between ACE I/D polymorphisms and (T2DM+HTN). Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were applied to assess the strength of association. The RevMan5.3 software was applied for heterogeneity test and combined ORs and their 95% CIs calculation. Publication bias was assessed through funnel plot.Results Nine case-control studies on the relationship between ACE I/D polymorphisms and T2DM + HTN were included,involving 554 patients (T2DM+HTN) and 664 controls (T2DM without HTN). The combined OR (95% CI) for ACE gene (DD VS Ⅱ), (ID VS Ⅱ), (DD+ID VS Ⅱ), (DD VS Ⅱ+ID) genotypes and D allele were 1. 77 (1. 28 ～ 2. 45),1. 19 (0. 90 ～1.57),1.28 (0. 84 ～ 1. 94),1. 55 (0. 97 ～ 2. 46) and1.36 (1. 04 ～ 1. 78),respectively. The corresponding P were < 0. 01,0. 22,0. 25,0. 07 and 0. 02. No significant publication bias was detected by funnel plot and sensitivity analysis suggested the robustness of the results. Conclusion The insertion/deletion polymorphism of ACE gene may be associated with the increased risk of T2DM+HTN.
Objective To evaluate the relationship between angiotensin converting enzyme (ACE)insertion/deletion (I/D) polymorphisms and the risk of type 2 diabetes mellitus combined with hypertension (T2DM+ HTN). Methods Relevant literatures were extensively searched by using PubMed,Wanfang Databases,CNKI and VIP for collecting the case-control studies investigating the relationship between ACE I/D polymorphisms and (T2DM+HTN). Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were applied to assess the strength of association. The RevMan5.3 software was applied for heterogeneity test and combined ORs and their 95% CIs calculation. Publication bias was assessed through funnel plot.Results Nine case-control studies on the relationship between ACE I/D polymorphisms and T2DM + HTN were included,involving 554 patients (T2DM+HTN) and 664 controls (T2DM without HTN). The combined OR (95% CI) for ACE gene (DD VS Ⅱ), (ID VS Ⅱ), (DD+ID VS Ⅱ), (DD VS Ⅱ+ID) genotypes and D allele were 1. 77 (1. 28 ～ 2. 45),1. 19 (0. 90 ～1.57),1.28 (0. 84 ～ 1. 94),1. 55 (0. 97 ～ 2. 46) and1.36 (1. 04 ～ 1. 78),respectively. The corresponding P were < 0. 01,0. 22,0. 25,0. 07 and 0. 02. No significant publication bias was detected by funnel plot and sensitivity analysis suggested the robustness of the results. Conclusion The insertion/deletion polymorphism of ACE gene may be associated with the increased risk of T2DM+HTN.
引文
[1]赵爽,武英,李云,等.血管紧张素转换酶基因多态性与高血压合并糖尿病关系的研究[J].慢性病学杂志,2015,16(1):9-11.
[2]Al-Saikhan FI,Abd-Elaziz MA,Ashour RH.Association between risk of type 2 diabetes mellitus and angiotensin-converting enzyme insertion/deletion gene polymorphisms in a Saudi Arabian population[J].Biomed Rep,2017,7(1):56-60.
[3]Hussain M,Awan FR,Gujjar A,et al.A case control association study of ACE gene polymorphism(I/D)with hypertension in Punjabi population from Faisalabad,Pakistan[J].Clin Exp Hypertens,2018,40(2):186-191.
[4]Singh M,Singh AK,Singh S,et al.Angiotensin-converting enzyme gene I/D polymorphism increases the susceptibility to hypertension and additive diseases:a study on North Indian patients[J].Clin Exp Hypertens,2016,38(3):305-311.
[5]Alsafar H,Hassoun A,Almazrouei S,et al.Association of angiotensin converting enzyme insertion-deletion polymorphism with hypertension in emiratis with type 2 diabetes mellitus and its interaction with obesity status[J].Dis Markers,2015,2015:536041.
[6]Negi V S,Devaraju P,Gulati R.Angiotensin-converting enzyme(ACE)gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis[J].Clin Rheumatol,2015,34(9):1545-1549.
[7]许玲,任建民,马玉燕,等.血管紧张素Ⅰ转化酶基因多态和2型糖尿病高血压相关性的研究[J].山东医科大学学报,1999,37(2):147-148.
[8]曾昭淳,蒋涛,汪恕萍.ACE基因多态性,血清水平与2型糖尿病,2型糖尿病伴高血压的关系[J].重庆医科大学学报,2000,25(3):231-233.
[9]李英,张艳玲,孙述强,等.血管紧张素转换酶基因多态性与2型糖尿病并发高血压的相关性研究[J].临床心血管病杂志,2000,16(6):259-261.
[10]许岚,邓振霞,何戎华,等.血管紧张素转换酶基因多态性与2型糖尿病合并高血压的相关性研究[J].镇江医学院学报,2001,11(4):439-441.
[11]冼苏,廖蕴华,罗佐杰,等.2型糖尿病合并高血压与血管紧张素转化酶Ⅰ基因多态性的相关性及其脂质代谢的研究[J].广西医科大学学报,2002,19(4):459-461.
[12]周琳,薛耀明,高方,等.ACE基因的插入/缺失多态性与2型糖尿病伴高血压的相互关系[J].第一军医大学学报,2002,22(9):808-810.
[13]Nakhjavani M,Esfahanian F,Jahanshahi A,et al.The relationship between the insertion/deletion polymorphism of the ACEgene and hypertension in Iranian patients with type 2 diabetes[J].Nephrol Dial Transplant,2007,22(9):2549-2553.
[14]Ramachandran V,Ismail P,Stanslas J,et al.Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects[J].J Renin Angiotensin Aldosterone Syst,2008,9(4):208-214.
[15]Kumar R,Singh VP,Baker KM.The intracellular renin-angiotensin system in the heart[J].Curr Hypertens Rep,2009,11(2):104-110.
[16]Sayed-Tabatabaei FA,Oostra BA,Isaacs A,et al.ACE polymorphisms[J].Circ Res,2006,98(9):1123-1133.
[17]Mizuiri S,Hemmi H,Kumanomidou H,et al.Angiotensin converting enzyme(ACE)I/D genotype and renal ACE gene expression[J].Kidney Int,2001,60(3):1124-1130.
[18]Elshamaa MF,Sabry SM,Bazaraa HM,et al.Genetic polymorphism of ACE and the angiotensinⅡtype1 receptor genes in children with chronic kidney disease[J].J Inflamm(Lond),2011,8(1):20.
[19]Sun F,He N,Zhang K,et al.Association of ACE gene A2350Gand I/D polymorphisms with essential hypertension in the northernmost province of China[J].Clin Exp Hypertens,2018,40(1):32-38.
[20]Rana G,Yadav S,Joshi S,et al.Association of DD genotype of angiotensin-converting enzyme gene(I/D)polymorphism with hypertension among a North Indian population[J].J Community Genet,2018,9(1):51-55.
[2]Al-Saikhan FI,Abd-Elaziz MA,Ashour RH.Association between risk of type 2 diabetes mellitus and angiotensin-converting enzyme insertion/deletion gene polymorphisms in a Saudi Arabian population[J].Biomed Rep,2017,7(1):56-60.
[3]Hussain M,Awan FR,Gujjar A,et al.A case control association study of ACE gene polymorphism(I/D)with hypertension in Punjabi population from Faisalabad,Pakistan[J].Clin Exp Hypertens,2018,40(2):186-191.
[4]Singh M,Singh AK,Singh S,et al.Angiotensin-converting enzyme gene I/D polymorphism increases the susceptibility to hypertension and additive diseases:a study on North Indian patients[J].Clin Exp Hypertens,2016,38(3):305-311.
[5]Alsafar H,Hassoun A,Almazrouei S,et al.Association of angiotensin converting enzyme insertion-deletion polymorphism with hypertension in emiratis with type 2 diabetes mellitus and its interaction with obesity status[J].Dis Markers,2015,2015:536041.
[6]Negi V S,Devaraju P,Gulati R.Angiotensin-converting enzyme(ACE)gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis[J].Clin Rheumatol,2015,34(9):1545-1549.
[7]许玲,任建民,马玉燕,等.血管紧张素Ⅰ转化酶基因多态和2型糖尿病高血压相关性的研究[J].山东医科大学学报,1999,37(2):147-148.
[8]曾昭淳,蒋涛,汪恕萍.ACE基因多态性,血清水平与2型糖尿病,2型糖尿病伴高血压的关系[J].重庆医科大学学报,2000,25(3):231-233.
[9]李英,张艳玲,孙述强,等.血管紧张素转换酶基因多态性与2型糖尿病并发高血压的相关性研究[J].临床心血管病杂志,2000,16(6):259-261.
[10]许岚,邓振霞,何戎华,等.血管紧张素转换酶基因多态性与2型糖尿病合并高血压的相关性研究[J].镇江医学院学报,2001,11(4):439-441.
[11]冼苏,廖蕴华,罗佐杰,等.2型糖尿病合并高血压与血管紧张素转化酶Ⅰ基因多态性的相关性及其脂质代谢的研究[J].广西医科大学学报,2002,19(4):459-461.
[12]周琳,薛耀明,高方,等.ACE基因的插入/缺失多态性与2型糖尿病伴高血压的相互关系[J].第一军医大学学报,2002,22(9):808-810.
[13]Nakhjavani M,Esfahanian F,Jahanshahi A,et al.The relationship between the insertion/deletion polymorphism of the ACEgene and hypertension in Iranian patients with type 2 diabetes[J].Nephrol Dial Transplant,2007,22(9):2549-2553.
[14]Ramachandran V,Ismail P,Stanslas J,et al.Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects[J].J Renin Angiotensin Aldosterone Syst,2008,9(4):208-214.
[15]Kumar R,Singh VP,Baker KM.The intracellular renin-angiotensin system in the heart[J].Curr Hypertens Rep,2009,11(2):104-110.
[16]Sayed-Tabatabaei FA,Oostra BA,Isaacs A,et al.ACE polymorphisms[J].Circ Res,2006,98(9):1123-1133.
[17]Mizuiri S,Hemmi H,Kumanomidou H,et al.Angiotensin converting enzyme(ACE)I/D genotype and renal ACE gene expression[J].Kidney Int,2001,60(3):1124-1130.
[18]Elshamaa MF,Sabry SM,Bazaraa HM,et al.Genetic polymorphism of ACE and the angiotensinⅡtype1 receptor genes in children with chronic kidney disease[J].J Inflamm(Lond),2011,8(1):20.
[19]Sun F,He N,Zhang K,et al.Association of ACE gene A2350Gand I/D polymorphisms with essential hypertension in the northernmost province of China[J].Clin Exp Hypertens,2018,40(1):32-38.
[20]Rana G,Yadav S,Joshi S,et al.Association of DD genotype of angiotensin-converting enzyme gene(I/D)polymorphism with hypertension among a North Indian population[J].J Community Genet,2018,9(1):51-55.