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J Hum Genet. 2007;52(9):757-62. Epub 2007 Aug 9.

The association of common polymorphisms in the QPCT gene with bone mineral density in the Chinese population.

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  • 1Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong. huangqy@hkucc.hku.hk


Evidence of the linkage of chromosome 2p to bone mineral density (BMD) has previously been reported in multiple populations. However, the identification of the BMD quantitative trait loci (QTL) gene at chromosome 2p remains a challenge. We performed a gene-wide and tag single nucleotide polymorphism (SNP)-based association study of four positional and functional candidate genes (CALM2, CYP1B1, QPCT, and POMC) in a sample of 1,243 cases and matched controls. Thirteen HapMap tag SNPs were selected and genotyped by using the high-throughput Sequenom genotyping platform. Binary logistic regression analyses were performed to test for associations between each SNP genotype and BMD. Haplotype association analyses were performed by WHAP. The rs3770748 within the QPCT gene showed a significant association with spine BMD in both single-marker (P = 0.002) and haplotype association analyses (P = 0.0482 for the global test; P = 0.00092 for the haplotype-specific test). Subgroup analysis revealed that the effect was primarily driven by an association in the postmenopausal women, presumably suggesting that the rs3770748 affects postmenopausal bone loss rather than peak bone mass. Our results suggest that QPCT may be the QTL gene at chromosome 2p for spine BMD variation in the Chinese population.

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