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 offspring's 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. RFCI 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 genenutrient interaction between offspring RFC1 genotype and periconceptional intake of folic acid on the risk of congenital heart defects.