The Sp1 COLIA1 gene polymorphism, and not vitamin D receptor or estrogen receptor gene polymorphisms, determines bone mineral density in postmenopausal Greek women

Several genetic polymorphisms are implicated as determinants of bone minera l density (BMD) in postmenopausal women. These include the Sp1 polymorphism of the collagen type I alpha 1 (COLIA1) gene, the FokI and BsmI polymorphi sms of the vitamin D receptor (VDR) gene, and the PvuII and XbaI polymorphi sms of the estrogen receptor (ER) gene. The relative importance and the ind ependence of these genetic effects have not been studied simultaneously in the same population. We evaluated the effects of these polymorphisms on lum bar spine BMD among 154 postmenopausal Greek women. BMD tended to differ ac ross Spl genotypes (mean 0.842 g/cm(2) in SS, 0.851 g/cm(2) in Ss, 0.763 in ss, age-adjusted p = 0.056), mostly because ss homozygotes had lower BMD ( p = 0.018 compared with SS and Ss). No other polymorphisms were associated with BMD in this population (p = 0.53 for FokI, p = 0.94 for BsmI, p = 0.80 for PvuII, p = 0.91 for XbaI). In multivariate modeling, the effect of ss homozygosity was clinically and statistically si,significant (-0.105 g/cm(2 ), p = 0.013) after adjusting for age, weight, height, hormone replacement use, and the other four polymorphisms. None of the other four polymorphisms was retained as an independent predictor of BMD in a backward elimination model and no significant synergistic effects were observed when gene intera ctions were tested. When all five polymorphisms are considered simultaneous ly, the Spl COLIA1 polymorphism seems to have the most unequivocal effect o n BMD, at least in postmenopausal women.