The Association Between Renin-Angiotensin System Gene Polymorphisms And Risk Of Childhood Hypertension:A Systematic Review And Meta-Analysis

Objective To explore the association between the genetic markers angiotensin converting enzyme (ACE) I/D, angiotensinogen (ANG) M235T and angiotensin Ⅱ receptor-1 (AT1R) A1 166C and risk of hypertension in pediatric subjects.Methods EMBASE, PubMed, 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 March lth 2016. Data extraction, quality assessment, pooled analysis was 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 was performed. Statistical analyses were analyzed by Stata12.0 software.Results A total of 969 patients and 1875 controls in 8 studies with moderate bias risk were included. An increased risk of ACE (I/D) D variant with 7 included studies in the meta-analysis under recessive model (OR=1.355, 95%CI=1.063-1.727, P=0.014) and dominant model (OR=1.369,95%CI =1.080-1.736, P=0.009). Neither ANG M235T polymorphism with 4 enrolled studies nor AT1R A1166C polymorphism with 3 enrolled studies was found to have significant association with hypertension in pediatric population under recessiveness, dominance, co-dominance, addition and 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.Conclusions No significant association was found between ANG M235T, AT1R A1166C polymorphisms and hypertension in pediatric population. The ACE I/D polymorphism might be associated with susceptibility to hypertension in the obese pediatric population.