Garnero P, Borel O, Grant S F, Ralston S H, Delmas P D
INSERM Unit 403, Hôpital E. Herriot, Lyon, France.
J Bone Miner Res. 1998 May;13(5):813-7. doi: 10.1359/jbmr.1998.13.5.813.
Bone mineral density (BMD) is under strong genetic control. Recent work has suggested that a polymorphism affecting an Sp1 binding site in the collagen I (COLI) A1 gene is associated with BMD and vertebral fracture in postmenopausal women. We analyzed this polymorphism in relation to BMD and bone turnover in 220 healthy premenopausal women aged 31-57 years. There were 61% SS homozygotes, 35% Ss heterozygotes, and 4% ss homozygotes, genotype frequencies similar to those previously reported in other Caucasian populations. Women in the three genotype groups were matched for age, body weight, physical activity, smoking habits, and oral contraceptive use, but height was greatest in the SS group and lowest in the ss group (p = 0.03). Between-group comparisons by analysis of variance (ANOVA) showed that COLI A1 genotype was significantly associated with spine BMD (p = 0.05), total body BMD (p = 0.046), and total body bone mineral content (BMC) (p = 0.02), but the differences between extreme genotypes were small (4, 5, and 10%, for spine BMD, total body BMD, and total body BMC, respectively). After adjustment for height, the differences between genotypes decreased and were no longer significant by ANOVA (p = 0.08, 0.17, and 0.33 for spine BMD, total body BMD, and total body BMC). Furthermore, no significant difference between genotypes was observed for femoral neck, trochanter, Ward's triangle, or forearm BMD. COLI A1 genotype was associated with serum C-terminal extension propeptide of type I collagen (p = 0.04), with lowest levels in ss individuals, but not with any other marker of bone formation (osteocalcin, alkaline phosphatase, and type I collagen N-terminal extension propeptide) or bone resorption (urinary excretion of type I collagen C and N telopeptide breakdown products). The COLI A1 Sp1 polymorphism is associated with height, peak total body BMD and BMC, and spine BMD. The genotype-specific differences account for only a small proportion of variance in BMD at these sites and are not significant after adjustment for height, suggesting that part of the effect on bone mass may be due to differences in body size. Our data support the view that COLI A1 may be a candidate gene for regulation of bone mass, but our results must be treated with caution, in view of the small number of ss individuals, and will require confirmation in larger studies.
骨密度（BMD）受强大的基因控制。最近的研究表明，影响I型胶原（COLI）A1基因中一个Sp1结合位点的多态性与绝经后女性的骨密度和椎体骨折有关。我们分析了220名年龄在31 - 57岁的健康绝经前女性中该多态性与骨密度和骨转换的关系。其中61%为SS纯合子，35%为Ss杂合子，4%为ss纯合子，基因型频率与先前在其他白种人群体中报道的相似。三个基因型组的女性在年龄、体重、身体活动、吸烟习惯和口服避孕药使用方面进行了匹配，但身高在SS组最高，在ss组最低（p = 0.03）。通过方差分析（ANOVA）进行组间比较显示，COLI A1基因型与脊柱骨密度（p = 0.05）、全身骨密度（p = 0.046）和全身骨矿物质含量（BMC）（p = 0.02）显著相关，但极端基因型之间的差异较小（脊柱骨密度、全身骨密度和全身BMC分别为4%、5%和10%）。在调整身高后，基因型之间的差异减小，经ANOVA分析不再显著（脊柱骨密度、全身骨密度和全身BMC的p值分别为0.08、0.17和0.33）。此外，在股骨颈、大转子、Ward三角区或前臂骨密度方面，未观察到基因型之间的显著差异。COLI A1基因型与I型胶原血清C末端延长肽相关（p = 0.04），在ss个体中水平最低，但与任何其他骨形成标志物（骨钙素、碱性磷酸酶和I型胶原N末端延长肽）或骨吸收标志物（I型胶原C和N端肽降解产物的尿排泄）均无关。COLI A1 Sp1多态性与身高、全身骨密度峰值和BMC以及脊柱骨密度相关。基因型特异性差异在这些部位的骨密度变异中仅占一小部分，在调整身高后不显著，这表明对骨量的部分影响可能归因于体型差异。我们的数据支持COLI A1可能是骨量调节候选基因的观点，但鉴于ss个体数量较少，我们的结果必须谨慎对待，并且需要在更大规模的研究中得到证实。
