Endothelial Nitric Oxide Synthase Gene Polymorphisms (G894T, 4b/a and T-786C) and Preeclampsia: Meta-Analysis of 18 Case-Control Studies

Studies investigating the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and preeclampsia reported contradictory or nonconclusive results. We performed a meta-analysis of 18 genetic association studies that examined the relationship between preeclampsia and the G894T, 4a/b and T-786C polymorphisms of the eNOS gene. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The MEDLINE, EMBASE, and Google Scholar databases were searched to access the relevant genetic association studies up to June 2011. For the allelic analysis of the G894T variant, all studies showed no significant association. For the genotypic analysis, the combined studies of the G allele showed negative significance (odds ratio [OR] = 0.56; 95% confidence interval [CI]: 0.33-0.97), all the studies showed positively significance when the T allele was combined (OR = 1.17; 95% CI: 1.01-1.36), and results were also positively significant in non-Asian populations (OR = 1.20; 95% CI: 1.02-1.43). For the allelic analysis of the 4b/a variant, all studies showed no significant association, but results were negatively significant in non-Asian populations (OR = 0.67; 95% CI: 0.46-0.98). For the genotype analysis, combined studies of the b allele showed negative significance (OR = 0.55; 95% CI: 0.36-0.84). Moreover, non-Asian studies showed negatively significant results (OR = 0.45; 95% CI: 0.28-0.72). For the analysis of the T-786C variant, none of the studies showed significant results. The synthesis of available evidence supports the fact that intron 4a allele, homozygosity for the 894T and intron 4a of eNOS are positively associated with preeclampsia. Large, multiethnic confirmatory, and well-designed studies are needed to determine the relation between preeclampsia and polymorphisms of the eNOS gene.