SNP Combinations in Chromosome-Wide Genes are Associated with Bone Mineral Density in Taiwanese Women

Gau-Tyan Lin ； Hung-Fu Tseng ； Chen-Kang Chang ； Li-Yeh Chuang ； Chih-Shan Liu ； Cheng-Hong Yang ； Chung-Jui Tu ； Eng-Chi Wang ； Hsiu-Fen Tan ； Chia-Che Chang ； Cheng-Hao Wen ； Hsiang-Chi Chen ； Hsueh-Wei Chang

《The Chinese Journal of Physiology》 51卷1期 (2008/02) Pp. 32-41

並列摘要

Osteoporosis is a major public health problem, mainly quantified by low BMD. Eleven polymorphisms were investigated in this study; TNFα-857 (rs1799724), TGFβ1-509 (rs1800469), osteocalcin (rs1800247), TNFα-308 (rs1800629), PTH BstB I (rs6254), PTH Dra Ⅱ (rs6256), ⅠL-1ra (VNTR), HSP70 hom (rs2227956), HSP 70-2 (rs1061581), CTR (rs1801197), and BMP-4 (rs17563). The relationship between the combined polymorphisms in different genomic regions and BMD variation was investigated. Among the female subjects, the proportion of subjects with low BMD in low BMI group (≤ 18.50) was significantly higher than that of the middle (18.51-22.99) and high (≥ 23.00) BMI groups (P ＜ 0.05). In post-menopausal women, there was a significant association between low BMD and genotypes ranging from 2~7 SNPs. For two combined SNPs, the portion of subjects with low BMD was significantly higher in those with CC-AA genotypes in rs1799724-rs1800629, compared to those with non-CC-AA genotypes in post-menopausal women and the combination of all women. Similarly, part of the combined SNPs with rs1799724-rs1800629-rs6254-rs6256-IL-1ra-rs2227956-rs1801197 was significantly associated with reduced BMD. After controlling for age and BMI, post-menopausal women with certain specific SNP combination had a 3.54- to 4.68-fold increased risk for low BMD, comparing to other SNP combinations. In conclusion, our data suggest that several gene polymorphisms may be cooperatively involved in the development of osteoporosis.

並列關鍵字

SNP interaction ； BMD ； BMI ； association ； osteoporosis

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