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

Hsiao-Ling Yang,S Shiao,Ya-Ling Yang,Chong Yu

doi:10.3390/ijerph15081660

Abstract

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 methylene-tetrahydrofolate reductase (MTHFR) 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 MTHFR 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 MTHFR 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 MTHFR 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 MTHFR 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 (p = 0.07). Our findings may have significant implications for inflammatory pathways in association with MTHFR polymorphisms and future intervention studies to correct for folate-related enzyme deficits resulted from MTHFR polymorphisms to prevent CHDs for future generations.

Highlights

Congenital heart disease (CHD) is the most common congenital abnormity and causes most mortality in children worldwide [1,2]
Our findings may have significant implications for inflammatory pathways in association with Methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms and future intervention studies to correct for folate-related enzyme deficits resulted from MTHFR
Methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms have been associated with many congenital anomalies including neural tube defects, deformed organs and body structures, and congenital heart disease (CHD) [7]

Summary

Introduction

Congenital heart disease (CHD) is the most common congenital abnormity and causes most mortality in children worldwide [1,2]. 90% of CHD cases could grow up into adulthood [3]. Many causes of CHD have been noted including chromosomal anomalies or gene mutations; maternal pregnancy complications including virus infection, various health conditions and teratogen drugs; and environmental factors including air pollutants [4,5,6]. It is imperative to better understand the effects of genetic and environmental factors on the development of CHD in order to prevent. Methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms have been associated with many congenital anomalies including neural tube defects, deformed organs and body structures, and CHD [7]. MTHFR polymorphisms affects folate metabolism in the one carbon metabolism (OCM)

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Discussion

Conclusion