Association of reduced folate carrier gene polymorphism and maternal folic acid use with neural tube defects

Am J Med Genet B Neuropsychiatr Genet. 2009 Sep 5;150B(6):874-8. doi: 10.1002/ajmg.b.30911.


This study was designed to investigate whether the risk for neural tube defects (NTDs) was associated with reduced folate carrier gene (RFC1 A80G) polymorphism and/or with the interaction between the RFC1 gene and maternal periconceptional use of folic acid. One hundred four nuclear families with NTDs and 100 non-malformed control families were sampled to investigate the potential interaction between maternal or the offspring's RFC1 (A80G) genotypes and the maternal periconceptional use of folic acid through a population-based case-control study. RFC1 (A80G) genotypes were detected using PCR-restricted fragment length polymorphism (PCR-RFLP). Mother who had the GG genotype and did not take folic acid had an elevated risk for NTDs (OR = 5.43, 95% CI = 1.68-18.28) as compared to the mother who had AA or GA genotype and took maternal periconceptional folic acid. The interactive coefficient was 1.12 between maternal GG genotype and the periconceptional folic acid non-use. The risk for having an infant with NTDs was 8.80 (95% CI = 2.83-28.69) for offspring with the GG genotype, as compared to the offspring with AA or GA genotype among the mothers who did not take folic acid supplements. The interactive coefficient was 1.45 for offspring with the GG genotype and without maternal periconceptional supplementation of folic acid. Our findings suggest that there is a potential gene-environment interaction on the risk of NTDs between maternal or offspring RFC1 GG genotype and maternal periconceptional intake of folic acid. The RFC1 is likely to be an important candidate gene in folate transportation and RFC1 GG genotype (A80G) may be associated with an increased risk for NTDs in this Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Child
  • Child, Preschool
  • China
  • Dietary Supplements
  • Female
  • Folic Acid / administration & dosage*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Membrane Transport Proteins / genetics*
  • Neural Tube Defects / genetics*
  • Polymorphism, Genetic*
  • Preconception Care / methods*
  • Reduced Folate Carrier Protein
  • Risk Factors


  • Membrane Transport Proteins
  • Reduced Folate Carrier Protein
  • SLC19A1 protein, human
  • Folic Acid