The contribution of vitamin D receptor gene polymorphisms in osteoporosis and familial osteoporosis

It is well established that genetic factors play a major role in the pathog enesis of osteoporosis. Previous reports have suggested that vitamin D rece ptor (VDR) gene polymorphisms, particularly the BE, tt and AA genotypes, ar e associated with low bone mineral density (BMD). If these VDR genotypes ar e indeed an important determinant of BMD, then a population of related oste oporotic individuals (mother-daughter or sister-sister relationship) should have a high prevalence of the BE, tt or AA VDR genotypes. To test this hyp othesis we determined the VDR genotypes in 26 osteoporotic persons (age 44. 3 +/- 12.7 years, mean +/- SD) belonging to 12 families. Furthermore, for c omparison with existing studies, we applied the VDR genotype analysis in a population of 53 unrelated healthy subjects (age 45.2 +/- 9.8 years, mean /- SD) and 59 unrelated osteoporotic subjects (age 52.1 +/- 9.0 years, mean +/- SD). The menopausal status of the healthy and osteoporotic populations was pre-, peri- and mostly early postmenopausal. The proportions of the th ree genotypes, BE, tt and AA, within the 12 osteoporotic families were 15%, 12% and 27%, respectively, whereas the proportions of the other three homo zygous genotypes (bb, TT, aa) were 50%, 50% and 23%. The distribution of th e BE, tt and AA genotypes in the normal population was 21%, 21% and 36%, re spectively (vs bb, TT, aa: 36%, 38%, 21%), whereas in the osteoporotic popu lation it was 23%, 20% and 34% (vs bb, TT, aa: 27%, 34%, 14%). Our data ind icate that there is not a statistically significant (p>0.05) difference in the VDR genotype frequencies within osteoporotic families as compared with the same genotypes in the population of unrelated normal or osteoporotic su bjects. VDR genotype analysis showed no significant relation between VDR po lymorphisms and BMD or Z-score values at the lumbar spine. This study demon strates the lack of a heritability pattern between the BE, tt and PLA genot ypes and low BMD.