Background:
Fractures are a common childhood injury. Polymorphisms in the vitamin D receptor gene (VDR) are associated with fracture risk in adults however, studies in children are limited. Previous work in the Vitamin D in Pregnancy (VIP) cohort found that maternal 25(OH)D concentration was associated with decreased fracture risk in boys at early gestation. This study aimed to determine the association between the child’s VDR genotype and their childhood fracture risk and whether their VDR genotype modifies the effect of maternal vitamin D in utero.
Methods:
At birth, 402 mother-child pairs from the VIP study had at least one serum 25(OH)D measure during pregnancy and 341 children had deoxyribonucleic acid extracted from a blood spot on their Guthrie card to determine their VDR genotype. Offspring fractures were identified through examining radiological reports from birth (2002-2004) until December 31st 2012. Multivariable Cox regression models were developed to examine associations and interaction terms were tested to determine if there was an interaction between VDR and maternal vitamin D concentrations.
Results:
In total, 341 mother-child pairs had complete information. There was no significant association between the offspring’s VDR genotype (BsmI, ApaI, TaqI and FokI) and their fracture risk. There was evidence of the offspring’s FokI genotype modifying the effect of maternal vitamin D in boys at early gestation (p=0.025). The ff genotype in boys was associated with a decreased fracture risk at recruitment (adjusted HR 0.78; 95% CI 0.64-0.96; p=0.021), while the FF and Ff genotypes were associated with increased fracture risk in girls (adjusted HR 1.02; 95% CI 1.00-1.03; p=0.042).
Conclusion:
Within this cohort, there is sexual dimorphism in the effects of the offspring’s VDR, specifically with the different FokI alleles between sexes mediating the action of maternal vitamin D in utero in opposing directions.