DESCRIPTION: (Adapted from Investigator's Abstract) Recently, common allelic variants in the gene encoding the vitamin D receptor (VDR) have been found to predict differences in bone density in an Australian population of 600 unrelated health women, and in 149 British twin pairs, but not in U.S. samples from Nebraska, Indianapolis or California. Such findings suggest a role for the VDR gene in the inheritance of osteoporosis, but further resolution of these conflicting studies is needed. Furthermore, there have been no studies to examine this gene in population-based cohorts, and the role of environmental factors among those with different allelic variants has not been defined. The objective of this project is to assess the association between osteoporosis and the allelic variants of the vitamin D receptor (VDR) using a randomly ascertained population-based cohort, the Framingham Study Cohort. Specifically, this project will determine the prevalence of the VDR alleles in the population using polymerase chain reaction (PCR) methods and restriction fragment length polymorphism (RFLP) among members of the original Framingham Study Cohort using DNA available from 1988-1989. To confirm that the inheritance of the VDR is co-dominant, the investigators will compare several measures of osteoporosis (bone mineral density scans, combined metacarpal cortical width, and the presence of vertebral fracture) among subjects in each of the three VDR genotypes. The measurements already have been obtained as part of the investigators' previous work on the Framingham Osteoporosis Study, and will permit determining if the VDR allele acts differently on trabecular bone than on cortical bone. Finally, the investigators will determine the impact of different environmental risk factors upon the expression of osteoporosis (measured at different skeletal sites) in those with or without the VDR alleles.
