TY - JOUR
T1 - Meta-prediction of MTHFR gene polymorphism and air pollution on the risks of congenital heart defects worldwide
T2 - A transgenerational analysis
AU - Yang, Hsiao Ling
AU - Yang, Ya Ling
AU - Yu, Chong Ho
AU - Shiao, S. Pamela K.
N1 - Funding Information:
supports include Research Start-up fund from Augusta University awarded to the corresponding author.
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/8/5
Y1 - 2018/8/5
N2 - 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 resultied from MTHFR polymorphisms to prevent CHDs for future generations.
AB - 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 resultied from MTHFR polymorphisms to prevent CHDs for future generations.
KW - Air pollution
KW - Congenital
KW - Heart defect
KW - Meta-predictive analysis
KW - Methylenetetrahydrofolate reductase
KW - Polymorphism
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U2 - 10.3390/ijerph15081660
DO - 10.3390/ijerph15081660
M3 - Article
AN - SCOPUS:85051368116
SN - 1661-7827
VL - 15
JO - International journal of environmental research and public health
JF - International journal of environmental research and public health
IS - 8
M1 - 1660
ER -
