• spina bifida;
  • betaine;
  • homocysteine;
  • folate;
  • polymorphism


Neural tube defects (NTD) are common malformations resulting from incomplete closure of the neural tube in the first month after conception. Since genetic deficiencies in folate-dependent homocysteine metabolism have been identified in NTD families, we investigated a common variant in betaine-homocysteine methyltransferase (BHMT), 742G[RIGHTWARDS ARROW]A (R239Q), as a genetic modifier of NTD risk. Genotypes, nutrient levels, and plasma total homocysteine (tHcy) were assessed in 54 patients with spina bifida, 57 mothers of patients, 93 control children, and 86 mothers of controls. The QQ genotype (present in 17% and 7% of the control and case mothers, respectively, and in 12% and 6% of the control and case children, respectively) was associated with a decreased risk of NTD (odds ratios of 0.52 (95% CI 0.13–2.05) for children and 0.37 (95% CI 0.11–1.22) for mothers). The small sample size limited the statistical power of the analyses, but these decreases, although not statistically significant, are compatible with a protective effect. We did not observe statistically-significant genotype-dependent differences in plasma homocysteine, although women with the QQ genotype did have lower homocysteine; in children, the mean homocysteine level was higher in the QQ group. This inconsistency could be explained by the fact that age is a strong determinant of homocysteine in children and the QQ group was on average older than the other genotype groups. Our study suggests that the Q allele of the R239Q mutation may decrease risk of the condition. This warrants further investigation of its relationship with the development of NTD. © 2003 Wiley-Liss, Inc.