A LARGE-SCALE POPULATION-BASED STUDY OF THE ASSOCIATION OF VITAMIN-D-RECEPTOR GENE POLYMORPHISMS WITH BONE-MINERAL DENSITY

Conflicting results have been reported on the association between rest riction fragment length polymorphisms (RFLPs) at the vitamin D recepto r (VDR) gene locus (i.e., for BsmI, ApaI, and TaqI) and bone mineral d ensity (BMD). We analyzed this association in a large population-based sample (n = 1782) of men and women aged 55-80 years using a novel dir ect haplotyping polymerase chain reaction (PCR) test to monitor the th ree polymorphic sites simultaneously, The direct haplotyping test we d eveloped demonstrated a larger degree of genetic polymorphism at the V DR gene locus than described until now, None of the individual RFLPs w ere associated with BMD at the proximal femur, By analyzing allele dos e effects, we identified a VDR haplotype allele weakly associated with low BMD. This allele, as one representative of the group of b alleles , is different from the BsmI allele previously reported by other group s to be associated with Low BMD, This suggests allelic heterogeneity a t the VDR locus in relation to BMD, Our results indicate at most a sma ll effect of the VDR genotype on BMD in this elderly population, Since anonymous polymorphisms were analyzed, alternative explanations for o ur results include linkage to another nearby bone-metabolism related g ene.