Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity

Studies on polymorphisms of candidate genes and their association with bone mineral density (BMD) have been reported in many populations, but few have been reported in Chinese populations. We investigated polymorphisms of the following five commonly used markers of four prominent BMD candidate genes with the purpose of identifying useful genetic markers for osteoporosis genetic research in Chinese: the Sp1 and RsaI polymorphisms of the collagen type 1 alpha l (Col1a1) gene, the −174G/C promoter polymorphism of the interleukin 6 (IL-6) gene, the Asn363Ser polymorphism of the glucocorticoid receptor (GR) gene, and the T → C polymorphism in intron 5 of the transforming growth factor β1 (TGF-β1) gene. We evaluated these polymorphisms using PCR-RFLP in samples of at least 124 random individuals. We compared the polymorphisms of these five markers with other populations using the χ2 test and Fisher's exact two-tailed test. For the RsaI polymorphism, only three heterozygotes but no variant homozygote were identified. For the −174G/C polymorphic site, only one GC heterozygote and no CC homozygote were found. Alleles s, Ser, and A 1 at the Sp1, Asn363Ser, and T → C marker sites that have been found to be polymorphic in other populations were not found in Chinese. Significant differences of allele and genotype frequency distributions were observed at these polymorphisms (P < 0.001) after comparing with other populations. Our results suggest that variant alleles of the five markers are absent or too rare to be useful genetic makers in Chinese, despite the fact that they have been commonly used as polymorphic markers in osteoporosis genetic research in other populations.