The (GT) n polymorphism and haplotype of theCOL1A2gene, but not the (AAAG) n polymorphism of thePTHR1gene, are associated with bone mineral density in Chinese.

Collagen type I a2 (COL1A2) and parathyroid hormone (PTH)/PTH-related peptide receptor (PTHR1) are two prominent candidate genes for bone mineral density (BMD). To test their importance for BMD variation in Chinese, we recruited 388 nuclear families composed of both parents and at least one healthy daughter with a total of 1,220 individuals, and simultaneously analyzed population stratification, total-family association, and within-family association between BMD at the spine and hip and the(GT) _n marker in the intron 1 of theCOL1A2gene and the(AAAG) _n marker in theP3promoter ofPTHR1gene. We also performed these association analyses with haplotypes of theMspI and (GT) _n polymorphisms in theCOL1A2gene. Significant within-family association was found between theM(GT) ₁₂ haplotype and trochanter BMD (P<0.001). Individuals with this haplotype have, on average, 9.53% lower trochanter BMD than the non-carriers. Suggestive evidence of the within-family association was detected between the(GT) ₁₇ allele and BMD at the spine (P=0.012), hip (P=0.011), femoral neck (P=0.032), trochanter (P=0.023), and intertrochanter (P=0.034). The association was confirmed by subsequent permutation tests. For the association, the proportion of phenotypic variance explained by the detected markers ranged from 1.2 to 3.9%, with the highest 3.9% at the trochanter for theM(GT) ₁₂ haplotype. This association indicates that there is strong linkage disequilibrium between the polymorphisms (MspI and GT repeat polymorphism) in theCOL1A2gene and a nearby quantitative trait locus (QTL) underlying BMD variation in Chinese, or the markers themselves may have an important effect on the variation of BMD. On the other hand, no significant within-family association, population stratification and total-family association between thePTHR1polymorphism and BMD were found in our Chinese population. [ABSTRACT FROM AUTHOR]