SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women.
Osteoporosis is a major public health problem, mainly quantified by low BMD. Eleven polymorphisms were investigated in this study; TNFalpha-857 (rs1799724), TGFbeta1-509 (rs1800469), osteocalcin (rs1800247), TNFalpha-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 (< or = 18.50) was significantly higher than that of the middle (18.51-22.99) and high (> or = 23.00) BMI groups (P < 0.05). In post-menopausal women, there was a significant association between low BMD and genotypes ranging from 2 to approximately 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.
Lin
Gau-Tyan
GT
Department of Orthopaedic Surgery, Chung-Ho Memorial Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
Tseng
Hung-Fu
HF
Chang
Chen-Kang
CK
Chuang
Li-Yeh
LY
Liu
Chih-Shan
CS
Yang
Cheng-Hong
CH
Tu
Chung-Jui
CJ
Wang
Eng-Chi
EC
Tan
Hsiu-Fen
HF
Chang
Chia-Che
CC
Wen
Cheng-Hao
CH
Chen
Hsiang-Chi
HC
Chang
Hsueh-Wei
HW
D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D015519:Bone Density; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide