肾素-血管紧张素系统基因多态性与儿童青少年高血压易感关联的系统评价和Meta分析

The association between renin-angiotensin gene polymorphisms and risk of childhood hypertension : a systematic review and meta-analysis

目的评价肾素-血管紧张素系统中的血管紧张素转换酶（ACE）基因插入/缺失（I/D）、血管紧张素原（ANG）基因M235T和血管紧张素Ⅱ受体-1（AT1R）基因A1166C多态性与儿童青少年高血压易感的关联。方法计算机检索EMBASE、Pub Med、HUGE、中国知网、维普数据库、万方数据库和中国生物医学文献数据库,检索时间均为建库至2015年11月27日,纳入3个基因多态性与儿童青少年高血压关联的病例对照研究。提取高血压组和对照组基因型和等位基因频率,行文献偏倚风险评价。采用Stata 12.0软件,分别以隐性、显性、共显性、相加和等位基因模型对高血压组和对照组上述3个基因多态性与高血压的关联行Meta分析。根据对照组人群和种族行亚组分析。结果 7篇文献进入Meta分析,病例组824例,对照组1 731例。7篇文献存在中等偏倚风险。1纳入6篇文献的ACE基因I/D多态性在隐性模型下与儿童青少年高血压的发病风险关联（OR=1.405,95%CI：1.073~1.840,P=0.013）。2上述5种分析模型,ANG基因M235T和AT1R基因A1166C多态性（分别纳入3和2篇文献）与儿童青少年高血压发病风险均无关联。3亚组分析结果显示,2篇文献肥胖人群的ACR基因I/D多态性在隐性、相加和等位基因模型下显著增加儿童青少年高血压的发病风险（隐性模型：OR=1.564,95%CI：1.054~2.321,P=0.026;相加模型：OR=2.017,95%CI：1.137~3.576,P=0.016;等位基因模型：OR=1.406,95%CI：1.076~1.838,P=0.013）。;对一般儿童青少年人群的高血压发病风险无影响,且与种族和高血压分类方法无关。结论 ANG基因M235T、AT1R基因A1166C多态性与儿童青少年高血压发病风险无关联,ACE基因I/D多态性可能与肥胖儿童青少年高血压的发病风险关联。

Objective To explore the association between the genetic markers angiotensin converting enzyme（ ACE）（ I / D）,angiotensinogen（ ANG）（ M235T） and angiotensin Ⅱ receptor-1 AT1R（ A1166C） and risk of hypertension in pediatric subjects.Methods EMBASE,Pub Med,Hartford User Group Exchange（ HUGE）,CNKI,VIP,Wanfang data and CBM database were searched for the case-control studies on the association of three gene polymorphisms with hypertension in pediatric patients from the establishment to November 27th2015. Data extraction,quality assessment and pooled analysis were conducted. Meta-analysis on the association of three gene polymorphisms with hypertension between hypertension group and control group under recessiveness,dominance,co-dominance,addition and allele gene models were performed. Statistical analysis was performed by Stata 12. 0software. Results A total of 824 patients and 1 731 controls from 7 case-control studies with moderate bias risk were included. An association between hypertension and ACE（ I / D） D variant was identified in 6 included studies in the meta-analysis under recessive model（ OR = 1. 405,95% CI = 1. 073- 1. 840,P = 0. 013）. Neither ANG（ M235T） polymorphism in 3 enrolled studies nor AT1R（ A1166C） polymorphism in 2 enrolled studies was associated with hypertension in pediatric population under recessiveness,dominance,co-dominance,addition or allele gene models. Subgroup analysis revealed that ACE（ I / D） D variant was associated with an increased risk of hypertension in obese pediatric population under recessive model（ OR = 1. 564,95% CI： 1. 054- 2. 321,P = 0. 026）,additive model（ OR = 2. 017,95% CI： 1. 137- 3. 576,P = 0. 016） and allele model（ OR = 1. 406,95% CI：1. 076- 1. 838,P = 0. 013）. There were no significant differences in the frequencies distribution of ACE（ I / D） between two groups in general population by considering ethnicity and classification of hypertension. Conclusion No significant association was found between ANG M235 T, AT1 R A1166C polymorphisms and hypertension in pediatric population. The ACE（ I / D）polymorphism might be associated with susceptibility to hypertension in the obese pediatric population.