Effects of maternal genetic polymorphisms in vitamin D-binding protein and serum 25-hydroxyvitamin D concentration on infant birth weight

Objective Vitamin D deficiency is a common problem during pregnancy and might contribute to adverse birth outcomes. Vitamin D-binding protein plays a key role in regulating vitamin D metabolism. We investigated whether maternal genetic variation in GC, the gene encoding vitamin-D binding protein, modulates the relationship between 25-hydroxyvitamin D [25(OH)D] levels and infant birth weight. Methods We measured 25(OH)D concentrations in maternal and umbilical cord blood from 356 pregnant women and their infants by liquid chromatography tandem mass spectrometry. We extracted DNA from the maternal blood for genotyping GC single-nucleotide polymorphisms (SNPs). Results The 25(OH)D concentrations were significantly higher in the maternal blood than in the cord blood, although the concentrations from each source were positively correlated with one another among individuals. Maternal GC SNPs rs12512631 and rs7041 were not significantly associated with infant birth weight. On the other hand, the GC SNPs rs12512631 and rs7041 significantly modified the relationships between the maternal and cord-blood concentrations of 25(OH)D and birth weight. Low 25(OH)D levels in the maternal and cord blood were significantly associated with decreased birth weight among infants born to mothers carrying the rs12512631 ‘C’ allele but not in those born to mothers homozygous for the ‘T’ allele (P-interaction = 0.043 and 0.0008 for the maternal and cord blood, respectively). Low 25(OH)D levels in the cord blood were significantly associated with decreased birth weight only among infants born to mothers carrying the rs7041 ‘G’ allele (P-interaction = 0.009). Conclusions Our findings suggest that the interaction between 25(OH)D status and some maternal GC variants influence the birth weight of infants.