TNFRSF11B gene variants and bone mineral density in postmenopausal women in Malta

Abstract

A number of polymorphisms in various genes have been identified and associated with bone mineral density (BMD) and with an increased risk of osteoporosis. In this study, three single nucleotide polymorphisms (SNPs) within the TNFRSF11B gene were studied for association with an increased risk of osteoporosis in postmenopausal Maltese women (n=126). Analysis was performed by PCR restriction fragment length polymorphism (RFLP) while BMD at the lumbar spine, femoral neck, Ward's triangle and trochanter was measured by DEXA. No significant association was observed between genotypes and BMD for all polymorphisms studied within this gene. Homozygotes CC (T(950)-C) were observed to have the highest BMD at all anatomical sites although statistical significance was not reached when comparing the three genotypes. A statistical significant difference was observed in the distribution of genotype frequencies for this polymorphism between normal individuals and those that were either osteopenic or osteoporotic at one or both anatomical sites, with the TT genotype associated more frequently with low BMD. The T(950)-C and G(1181)-C polymorphisms were in strong linkage disequilibrium with each other but not with the A(163)-G polymorphism further upstream in the OPG promoter. Statistical significance was reached when constructing haplotypes, where the A-T-G haplotype was found to be more frequent in individuals with low BMD. These results indicate the possible role of TNFRSF11B gene variants in postmenopausal bone loss in women in Malta.