Abstract
Previous studies have examined the role of three NOS3 gene polymorphisms [G894T, T-786C, and the variable number of tandem repeats 4b/a (VNTR 4b/a)] in the susceptibility to preeclampsia with inconclusive findings. We therefore conducted an updated meta-analysis by including more studies. The most appropriate genetic model was chosen for each polymorphism by using a well-established method. Pooled results indicated that, compared with the GT + GG genotype, the TT genotype of G894T was associated with an increased risk of preeclampsia (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.21–1.77, P < 0.001; I2 = 40.2%). The CC genotype of T-786C was also associated with a higher risk of preeclampsia (OR = 1.30; 95% CI = 1.07–1.58, P = 0.034; I2 = 46.9%) than the CT + TT genotype. No association was found for VNTR 4b/a. Stratified analysis indicated that the increased risk was evident for high-quality studies both for G894T and T-786C, and for studies conducted among Caucasians and Africans for T-786C. However, the increased risk for T-786C among Africans needs further confirmation due to the high probability of false-positive reports. Our results suggested that G894T and T-786C polymorphisms, but not VNTR 4b/a, were associated with an increased risk of preeclampsia.
Highlights
The NOS3 gene is located on chromosome 7q35–36, with a length of 4.4 kb[7]
Prior probability 0.25 0.1 0.01 0.001 0.0001. In this meta-analysis, we examined the associations between the three NOS3 gene polymorphisms (G894T, T-786C, and variable number of tandem repeats (VNTR) 4b/a) and the preeclampsia risk
Our results provide evidence of a significantly increased risk for preeclampsia for G894T and T-786C polymorphisms, under the recessive genetic model
Summary
The gene comprises 26 exons that encode an mRNA of 4,052 nucleotides[7]. In 2013, two meta-analyses on the associations between these three polymorphisms and preeclampsia risk were published but with inconsistent results[11,12]. Since the publication of these meta-analyses, eleven new studies have been published[13,14,15,16,17,18,19,20,21,22,23]. We have performed an updated systematic review and meta-analysis, adding the recently published studies to further clarify the role of these three SNPs in susceptibility to preeclampsia and to address the limitations of the previous meta-analyses by using more sophisticated methods
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