Association of a polymorphism in the TNFR2 gene with low bone mineral density

Previous genetic linkage data suggested that a gene on chromosome 1p36.2-36 .3 might he linked to low bone mineral density (BMD). Here, we examine the gene for tumor necrosis factor receptor 2 (TNFR2), a candidate gene within that interval, for association with low BMD in a group of 159 unrelated ind ividuals. We assess two polymorphic sites within the gene, a microsatellite repeat within intron 4, and a three-nucleotide variation in the 3' untrans lated region (UTR) of the gene. The latter has five alleles of which the ra rest allele is associated with low spinal BMD Z score (p = 0.008). Lowest m ean spinal BMD Z scores were observed for individuals having genotypes that were heterozygous for the rarest allele, No homozygotes for the rarest all ele were observed. Preliminary analysis suggests that there is a difference in the genotype frequency distribution between the group with low BMD and a control group.