Genetic Variation of Infant Reduced Folate Carrier (A80G) and Risk of Orofacial Defects and Congenital Heart Defects in China

Purpose This study was designed to investigate whether the risks of congenital heart defects (CHD) and orofacial defects were influenced by a polymorphism of the offspringʹs RFC1 or by an interaction between the RFC1 gene and maternal periconceptional use of folic acid. Methods A case-control study was conducted. A total of 82 families with a child affected by cleft lip with or without cleft palate (CLP), 67 families with a child-affected by CHD, and 100 nonmalformed control families were genotyped using PCR-RFLP. RFC1 G allele was tested through family-based association test. Results Among mothers who did not use folic acid, the risks of 4.03 (95% CI = 1.33–12.77) for the G80/G80 genotype and 4.14 (95% CI = 1.06–16.82) for the G80/A80 genotype were observed relative to the A80/A80 genotype for CHD offspring. In family-based association tests (FBAT), offspring carrying the G allele for RFC1 is at increased risk for CHD (Z = 2.140, p < .05). No significant association was found between either RFC1 genotype or maternal folic acid supplementation and the risks of CLP. Conclusions Our findings suggest that the RFC1 G allele is likely to be an important candidate gene in folate transport and to be associated with risk for CHD. This study found modest evidence for a gene-nutrient interaction between offspring RFC1 genotype and periconceptional intake of folic acid on the risk of congenital heart defects.