Uitterlinden A G, Burger H, Huang Q, Yue F, McGuigan F E, Grant S F, Hofman A, van Leeuwen J P, Pols H A, Ralston S H
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
N Engl J Med. 1998 Apr 9;338(15):1016-21. doi: 10.1056/NEJM199804093381502.
Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type Ialpha1, a bone-matrix protein.
We determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of 1778 postmenopausal women using a polymerase-chain-reaction-based assay. We then related the genotypes to bone mineral density and the occurrence of osteoporotic fractures in these women.
As compared with the 1194 women with the SS genotype, the 526 women with the Ss genotype had 2 percent lower bone mineral density at the femoral neck (P=0.003) and the lumbar spine (P=0.02); the 58 women with the ss genotype had reductions of 4 percent at the femoral neck (P= 0.05) and 6 percent at the lumbar spine (P=0.005). These differences increased with age (P=0.01 for modification by age of the effect of COLIA1 on femoral-neck bone density, and P=0.004 for modification of the effect on lumbar-spine bone density). Women with the Ss and ss genotypes were overrepresented among the 111 women who had incident nonvertebral fractures (relative risk per copy of the s allele, 1.5; 95 percent confidence interval, 1.1 to 2.1).
The COLIA1 polymorphism is associated with reduced bone density and predisposes women to osteoporotic fractures.
骨质疏松症是一种常见疾病，具有很强的遗传因素。遗传因素可能表达的一种方式是通过I型胶原α1（一种骨基质蛋白）的基因COLIA1的多态性。
我们使用基于聚合酶链反应的检测方法，在1778名绝经后妇女的人群样本中确定了COLIA1的基因型SS、Ss和ss。然后我们将这些基因型与这些妇女的骨矿物质密度和骨质疏松性骨折的发生情况联系起来。
与1194名具有SS基因型的妇女相比，526名具有Ss基因型的妇女在股骨颈处的骨矿物质密度低2%（P = 0.003），在腰椎处低2%（P = 0.02）；58名具有ss基因型的妇女在股骨颈处降低了4%（P = 0.05），在腰椎处降低了6%（P = 0.005）。这些差异随着年龄增加而增大（COLIA1对股骨颈骨密度影响的年龄修正P = 0.01，对腰椎骨密度影响的年龄修正P = 0.004）。在111名发生非椎骨骨折的妇女中，具有Ss和ss基因型的妇女比例过高（s等位基因每拷贝的相对风险为1.5；95%置信区间为1.1至2.1）。
COLIA1多态性与骨密度降低相关，并使女性易患骨质疏松性骨折。
