Spina bifida and genetic factors related to myo-inositol, glucose, and zinc

Abstract

Background. Myo-inositol, glucose and zinc and related genetic factors are suggested to be implicated in the etiology of spina bifida. We investigated the biochemical concentrations of these nutrients and polymorphisms in the myo-inositol transporter SLC5A11, myo-inositol synthase ISYNA1, and zinc transporter SLC39A4 in association with spina bifida risk. Methods. Seventy-six spina bifida triads only were ascertained. In mothers, fathers, and spina bifida children polymorphisms determined were SLC5A11 (544C > T), ISYNA1 (1029A > G), and SLC39A4 (1069C > T). Serum myo-inositol and glucose, and red blood cell zinc concentrations were determined in mothers and spina bifida children. Transmission disequilibrium tests (TDT) were applied to determine associations between the polymorphisms and spina bifida. Associations between biochemical values and genotypes were studied by one-way analysis of variance (ANOVA). Interactions between alleles, biochemical values, and environmental factors were analyzed by conditional logistic regression. Results. No association between SLC5A11, ISYNA1, and SLC39A4 and spina bifida was shown, χ 2 SLC5A11=0.016, P=0.90; χ 2 SYNA1=1.52, P=0.22; χ 2 SLC39A4=0.016, P=0.90; and degrees of freedom (df)=1. Maternal glucose concentrations were comparable for the SLC5A11 genotypes. Significantly lower myo-inositol concentrations were observed in mothers with SLC5A11 CC-genotype, mean (SD) 14.2 (2.6) μmol/L compared to SLC5A11 TT-genotype, 17.0 (3.4) μmol/L, P<0.05. No significant associations were observed between ISYNA1 and myo-inositol and glucose, and between SLC39A4 and zinc. A significant interaction was demonstrated between a maternal glucose <4.5 mmol/L and ISYNA1 1029A > G polymorphism on spina bifida risk. Conclusion. The combination of maternal glucose <4.5 mmol/L and ISYNA1 1029A > G polymorphism protects against spina bifida offspring. Moreover, maternal SLC5A11 544C > T polymorphism contributes to the serum myo-inositol concentration. Larger studies should confirm these findings.