Association of maternal AGTR1 polymorphisms and preeclampsia: A systematic review and meta-analysis
ABSTRACT Objective: Systematic review and meta-analysis to investigate the association between maternal AGTR1 gene single nucleotide polymorphisms (SNPs) and preeclampsia (PE). Methods: A systematic literature search was performed using PubMed, EMBASE, Scopus, and HuGE Literature Finder databases. The review was conducted according to PRISMA guidelines. Summary odds ratios (ORs) for the allelic and genotypic contrasts were calculated and compared to indicate the most appropriate genetic model for the polymorphism of interest. Among-study heterogeneity was assessed using the I(2) statistic and publication bias was evaluated visually using funnel plots. Results: Seven maternal SNPs investigated with PE were found, but only AGTR1 +1166A>C accumulated sufficient evidence for meta-analysis. Summary ORs calculated from eight studies (10 populations involving 845 PE cases and 1150 controls) did not reveal an association between the +1166A>C polymorphism and PE (allelic OR = 1.19, 95% CI: 0.96-1.47). No evidence of publication bias and among-study heterogeneity was detected. Conclusions: meta-analysis findings did not support AGTR1 +1166A>C as a susceptibility locus for PE. Other AGTR1 SNPs require more study.
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ABSTRACT: The SERPINE1 -675 4G/5G promoter region insertion/deletion polymorphism (rs1799889) has been implicated in the pathogenesis of preeclampsia (PE), but the genetic association has been inconsistently replicated. To derive a more precise estimate of the association, a systematic review and meta-analysis was conducted. This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed (MEDLINE), Scopus, and HuGE Literature Finder literature databases were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CI) were calculated for the allelic comparison (4G vs. 5G) and genotypic comparisons following the co-dominant (4G/4G vs. 5G/5G & 4G/5G vs. 5G/5G), dominant (4G/4G+4G/5G vs. 5G/5G), and recessive (4G/4G vs. 4G/5G+5G/5G) genetic models. Between-study heterogeneity was quantified by I2 statistics and publication bias was appraised with funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. Meta-analysis of 11 studies involving 1297 PE cases and 1791 controls found a significant association between the SERPINE1 -675 4G/5G polymorphism and PE for the recessive genetic model (OR=1.36, 95% CI: 1.13-1.64, p=0.001), a robust finding according to sensitivity analysis. A low level of between-study heterogeneity was detected (I2=20%) in this comparison, which may be explained by ethnic differences. Funnel plot inspection did not reveal evidence of publication bias. In conclusion, this study provides a comprehensive examination of the available literature on the association between SERPINE1 -675 4G/5G and PE. Meta-analysis results support this polymorphism as a likely susceptibility variant for PE.Molecular Human Reproduction 11/2012; 19(3). DOI:10.1093/molehr/gas056 · 3.75 Impact Factor
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ABSTRACT: Pregnancy hypertensive disorders (PHDs) are considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the renin-angiotensin system are considered to play a significant role in the pathogenesis of the PHDs. However, results from published studies on the association between the angiotensin II type-1 receptor (AT1R) A1166C (rs5186) gene polymorphism and the risk of PHDs are conflicting. The aim of this meta-analysis was to investigate whether an association exists between AT1R A1166C gene polymorphism and PHDs in epidemiologic studies. We searched the PubMed, China National Knowledge Infrastructure (CNKI), and Chinese Biomedicine Literature (CBM) databases from their inception to July 2012. A total of 18 case-control studies, including a total of 1635 cases and 1934 controls, were available for this analysis. A significantly positive correlation was observed between the C allele and the AC/CC genotypes with PHDs in an overall comparison. In the subgroup analysis by ethnicity, the results suggested that the C allele and the AC/CC genotypes were associated with risk of PHDs in Asians. Our findings indicate that the AT1R gene 1166C allele and the AC/CC genotypes were positively associated with the PHDs, especially in Asians. However, well-designed multicenter studies with a larger sample size should be conducted to confirm the results.Journal of Renin-Angiotensin-Aldosterone System 12/2012; 15(2). DOI:10.1177/1470320312467556 · 2.40 Impact Factor
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ABSTRACT: Preeclampsia is a pregnancy specific disorder and a risk factor for later cardiovascular disease. The cause and detailed pathophysiology remains unknown. G protein signaling is involved in a variety of physiological processes, including blood pressure regulation. We assessed whether distributions of 3 single nucleotide polymorphisms in genes coding for components of G protein signaling pathways that have been associated with hypertension differ between women with preeclampsia and normotensive pregnant women; the G protein β3 subunit gene (GNB3) C825T polymorphism (rs5443), the angiotensin II type 1 receptor gene (AGTR1) 3'UTR A1166C polymorphism (rs5186), and the regulator of G protein signaling 2 gene (RGS2) 3'UTR C1114G polymorphism (rs4606). Two separate Norwegian study populations were used; a large population based study and a smaller, but clinically well-described pregnancy biobank. A descriptive study of 43 women with eclampsia was additionally included. In the population-based study, an increased odds of preeclampsia (odds ratio, 1.21; [95% confidence interval, 1.05-1.40]; P=0.009) and recurrent preeclampsia (odds ratio, 1.43; [95% confidence interval, 1.06-1.92];, P=0.017) was found in women carrying the rs4606 CG or GG genotype. In early-onset preeclamptic patients with decidual spiral artery biopsies available (n=24), the rs4606 CG or GG genotype was more frequent in those with acute atherosis (resembling early stage of atherosclerosis) compared with those without: odds ratio, 15.0; (95% confidence interval, 2.02-111.2); P=0.004. No association was found between preeclampsia and the rs5443 or the rs5186. The genotype distribution in eclamptic women was not different from preeclamptic women. In conclusion, RGS2 rs4606 may affect the risk and progression of preeclampsia.Hypertension 01/2013; 61(3). DOI:10.1161/HYPERTENSIONAHA.111.00331 · 6.48 Impact Factor