Meta-prediction of MTHFR gene polymorphisms and air pollution on the risk of hypertensive disorders in pregnancy worldwide

Hypertensive disorders in pregnancy (HDP) are devastating health hazards for both women and children. Both methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and air pollution can affect health status and result in increased risk of HDP for women. The major objective of this study was to investigate the effect of MTHFR polymorphisms, air pollution, and their interaction on the risk of HDP by using meta-predictive analytics. We searched various databases comprehensively to access all available studies conducted for various ethnic populations from countries worldwide, from 1997 to 2017. Seventy-one studies with 8064 cases and 13,232 controls for MTHFR C677T and 11 studies with 1425 cases and 1859 controls for MTHFR A1298C were included. MTHFR C677T homozygous TT (risk ratio (RR) = 1.28, p < 0.0001) and CT plus TT (RR = 1.07, p = 0.0002) were the risk genotypes, while wild-type CC played a protective role (RR = 0.94, p = 0.0017) for HDP. The meta-predictive analysis found that the percentage of MTHFR C677T TT plus CT (p = 0.044) and CT (p = 0.043) genotypes in the HDP case group were significantly increased with elevated levels of air pollution worldwide. Additionally, in countries with higher air pollution levels, the pregnant women with wild-type CC MTHFR 677 had a protection effect against HDP (p = 0.014), whereas, the homozygous TT of MTHFR C677T polymorphism was a risk genotype for developing HDP. Air pollution level is an environmental factor interacting with increased MTHFR C677T polymorphisms, impacting the susceptibility of HDP for women.