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

Abstract

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.

Polymorphisms of rs1799983 (G>T) and rs1800780 (A>G) of the eNOS gene associated with susceptibility to essential hypertension in the Chinese Hui ethnic population

“…In contrast, the rs2070744 (T>C) variant (T786C mutation) was reported to lack an association with EH in Chinese Kazakh and Japanese groups (Kajiyama et al, 2000;Deng et al, 2007). Consistent with these findings in other ethnic populations, such as Chinese Han (Niu et al, 2011;Chen et al, 2012), Hani (Tang et al, 2008), Yi (Tang et al, 2008), and Uygur (Zhang et al, 2006) in China, polymorphism of rs1799983 (G>T) in the eNOS gene was found to be a risk factor of EH, while rs2070744 (T>C) polymorphism lacked an association with EH, in the Chinese Hui ethnic population in this study. Notably, a positive correlation between rs1800780 (A>G) polymorphism and susceptibility to EH was determined here in the Chinese Hui group.…”

“…The EH diagnosis criteria of the World Health Organization (WHO) of 1999 was used to diagnose patients with EH (Chen et al, 2012). The non-EH controls were recruited from the general Hui population and had undergone comprehensive medical screening at the Hospital.…”

Genetic markers for prediction of early and late onset preeclampsia in pregnant women with preexisting type 1 diabetes mellitus

“…Если говорить о вошедшем в нашу комбинацию G894T полиморфизме гена eNOS, то, в соответствии с дан-ными современных исследований [43,45], присутствие причинных Т аллелей в генотипе беременных коррели-рует со снижением уровня оксида азота в их крови; при этом минимальные концентрации этого компонента ре-гистрируются у носителей ТТ-генотипа по данному поли-морфизму. Взаимосвязь между данным полиморфизмом и риском развития преэклампсии широко обсуждается в литературе и подтверждена целым рядом исследований [2,8,16,23,37,45].…”

Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?

“…However, results of these investigations are conflicting and controversial. Two meta-analyses [142,143] searched to clarify the associations between these genetic variants and the risk for PE. Chen et al [142] displayed in non-Asian populations (seven studies included) a positive significant association between the intron 4a allele and PE.…”

“…Two meta-analyses [142,143] searched to clarify the associations between these genetic variants and the risk for PE. Chen et al [142] displayed in non-Asian populations (seven studies included) a positive significant association between the intron 4a allele and PE. Moreover, homozygosity for the 894T and intron 4a of eNOS were significantly positively associated with PE, especially in non-Asian populations.…”