Garnero P, Borel O, Sornay-Rendu E, Arlot M E, Delmas P D
INSERM Unit 403, Hôpital E. Herriot, Lyon, France.
J Bone Miner Res. 1996 Jun;11(6):827-34. doi: 10.1002/jbmr.5650110614.
Vitamin D receptor (VDR) gene polymorphisms have been reported to account for most of the well established genetic influence on bone mineral density (BMD). However, discordant studies have been published and it is still not clear whether VDR genotypes influence bone mass accretion and/or postmenopausal bone loss. In this study, we analyzed VDR gene polymorphisms, i.e., that of BsmI, ApaI, and TaqI restriction enzymes in 268 untreated postmenopausal women 1-26 years postmenopausal. There were 37 BBAA homozygote (absence of BsmI and ApaI restriction sites on both alleles), 55 bbaa homozygote (presence of restriction sites on both alleles), and 176 heterozygotes. At baseline, women between the three genotypes did not differ significantly in age, years since menopause, body mass index (BMI), nor dietary calcium intake. We found no relationship between VDR genotypes and bone turnover assessed by three serum markers of bone formation and three urinary bone resorption markers, nor with BMD measured at the spine, hip, forearm, and whole body by dual-energy X-ray absorptiometry (DXA). Rates of bone loss assessed by repeated DXA measurements over 2 years were highly significant (p = 0.02-0.0001) at all skeletal sites except for the lumbar spine but did not differ between genotypes at any sites either before or after adjustment for potential confounding factors such as years since menopause, BMI, calcium intake, serum 25 hydroxyvitamin D levels, and baseline BMD. When we restricted the analysis to early postmenopausal women, within 10 years of menopause (n = 128), lumbar spine bone loss became significant, but no significant difference between VDR genotypes in the rate of bone loss measured at any site was found. We conclude that VDR genotypes are not predictive of bone turnover, rate of postmenopausal bone loss, and bone mass in either early or late postmenopausal women. In a subgroup of women with a low calcium intake (below 600 mg/day), we also found no significant differences between genotypes in BMD and the rate of bone loss measured at any site, although the sample size (n = 64) may be too small to detect small differences. In conclusion, these data, along with the absence of relationships between VDR gene polymorphisms and peak bone mass that we recently reported, suggest that the determination of VDR genotypes is probably not a useful clinical test for the risk assessment of osteoporosis.
维生素D受体（VDR）基因多态性据报道是对骨矿物质密度（BMD）产生既定遗传影响的主要因素。然而，已有不一致的研究发表，VDR基因型是否影响骨质积聚和/或绝经后骨质流失仍不清楚。在本研究中，我们分析了268名绝经后1至26年未经治疗的绝经后女性的VDR基因多态性，即BsmI、ApaI和TaqI限制性内切酶的多态性。有37名BBAA纯合子（两个等位基因均无BsmI和ApaI限制性位点）、55名bbaa纯合子（两个等位基因均有限制性位点）和176名杂合子。在基线时，三种基因型的女性在年龄、绝经年限、体重指数（BMI）和膳食钙摄入量方面均无显著差异。我们发现VDR基因型与通过三种骨形成血清标志物和三种尿骨吸收标志物评估的骨转换之间没有关系，也与通过双能X线吸收法（DXA）在脊柱、髋部、前臂和全身测量的BMD无关。通过重复DXA测量在2年内评估的骨质流失率在除腰椎以外的所有骨骼部位均高度显著（p = 0.02 - 0.0001），但在调整潜在混杂因素（如绝经年限、BMI、钙摄入量、血清25羟维生素D水平和基线BMD）之前或之后，各基因型在任何部位的骨质流失率均无差异。当我们将分析限制在绝经后10年内的早期绝经后女性（n = 128）时，腰椎骨质流失变得显著，但在任何部位测量的骨质流失率在VDR基因型之间未发现显著差异。我们得出结论，VDR基因型不能预测早期或晚期绝经后女性的骨转换、绝经后骨质流失率和骨量。在钙摄入量低（低于600毫克/天）的女性亚组中，我们也发现各基因型在任何部位的BMD和骨质流失率之间没有显著差异，尽管样本量（n = 64）可能太小，无法检测到微小差异。总之，这些数据，以及我们最近报道的VDR基因多态性与峰值骨量之间不存在关联，表明VDR基因型的测定可能不是骨质疏松症风险评估的有用临床检测方法。
