Zhang Yuan-Yuan, Lei Shu-Feng, Mo Xiao-Yang, Wang Yan-Bo, Li Miao-Xin, Deng Hong-Wen
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, 410081 Changsha, Hunan, P. R. China.
Calcif Tissue Int. 2005 Feb;76(2):107-12. doi: 10.1007/s00223-004-0110-4. Epub 2004 Nov 18.
Type I collagen is the most abundant protein of bone matrix, and the collagen type I alpha 1(COLIA1) gene has been considered one of the most important candidate genes for osteoporosis. In this study, we simultaneously tested linkage and/or association of the -1997 G/T polymorphism in the COLIA1 upstream regulatory region with the variation of bone mineral density (BMD) in 1263 subjects from 402 Chinese nuclear families, consisted of both parents and at least one healthy female offspring from 20 to 45 years of age. All the subjects were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD of the lumbar spine (L1-L4) and hip (respective and combined phenotype of the femoral neck, trochanter, and intertrochanter) was measured by dual-energy X-ray absorptiometry (DXA). By using the tests implemented in program QTDT (quantitative transmission disequilibrium test), we found significant within-family association (via TDT) between the -1997 G/T polymorphism with BMD variation at all the hip sites (respective and combined phenotypes, P < 0.05). The amount of BMD variation explained by the -1997G/T polymorphism was 1.6%, 2.0%, 1.2%, and 1.3% at the total hip, femoral neck, trochanter, and intertrochanter, respectively. Because of the limited number of sib pairs in this sample, we did not find evidence of linkage. In summary, the -1997 G/T polymorphism in the COLIA1 gene is likely to be in linkage disequilibrium with a nearby functional polymorphism affecting hip BMD, or the -1997 G/T polymorphism itself may have an important effect on the variation of hip BMD in our Chinese sample.
I型胶原蛋白是骨基质中含量最丰富的蛋白质，I型胶原蛋白α1（COLIA1）基因被认为是骨质疏松症最重要的候选基因之一。在本研究中，我们同时检测了COLIA1上游调控区-1997 G/T多态性与402个中国核心家庭中1263名受试者骨密度（BMD）变化的连锁和/或关联，这些家庭由父母和至少一名年龄在20至45岁的健康女性后代组成。所有受试者均采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型。采用双能X线吸收法（DXA）测量腰椎（L1-L4）和髋部（股骨颈、大转子和转子间的各自及合并表型）的骨密度。通过使用QTDT程序（定量传递不平衡检验）中实施的检验，我们发现-1997 G/T多态性与所有髋部部位的骨密度变化（各自及合并表型，P < 0.05）之间存在显著的家庭内关联（通过TDT）。-1997 G/T多态性解释的骨密度变化量在全髋、股骨颈、大转子和转子间分别为1.6%、2.0%、1.2%和1.3%。由于该样本中同胞对的数量有限，我们未发现连锁的证据。总之，COLIA1基因中的-1997 G/T多态性可能与影响髋部骨密度的附近功能多态性处于连锁不平衡状态，或者-1997 G/T多态性本身可能对我们中国样本中髋部骨密度的变化有重要影响。
