The -1997 G/T polymorphism in the COLIA1 upstream regulatory region is associated with hip bone mineral density (BMD) in Chinese nuclear families.

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.