Meta-Prediction of MTHFR Gene Polymorphism and Air Pollution on the Risks of Congenital Heart Defects Worldwide: A Transgenerational Analysis.

Congenital heart disease (CHD) is the leading cause of death in children, and is affected by genetic and environmental factors. To investigate the association of air pollution with () polymorphisms and the risk of CHD, we included 58 study groups of children and parents, with 12,347 cases and 18,106 controls worldwide. Both C677T (rs 1801133) and A1298C (rs 1801131) gene polymorphisms were risks for CHD in children with transgenerational effects from their parents. Countries with greater risks of CHD with a pooled risk ratio (RR) > 2 from 677 polymorphisms included Germany, Portugal, China, and Egypt for children; and Brazil, Puerto Rico, Mexico, China, and Egypt for mothers. Whereas, countries with greater risk of CHD with RR > 2 from 1298 polymorphisms included Taiwan, Turkey, and Egypt for children; and Brazil, China, and Egypt for mothers. Additionally, meta-prediction analysis revealed that the percentages of 677TT and TT plus CT polymorphisms together were increased in countries with higher levels of air pollution, with a trend of increased CHD risks with higher levels of air pollution for children ( = 0.07). Our findings may have significant implications for inflammatory pathways in association with polymorphisms and future intervention studies to correct for folate-related enzyme deficits resultied from polymorphisms to prevent CHDs for future generations.