Four Candidate Genes And Related Factors Of Bone Mineral Density In Chinese

Osteoporosis is a serious healthy disease, which is characterized by low bone mineral density (BMD) and deterioration of skeletal microarchitecture, leading to increased risk of fragility fracture. Low BMD is recognized as a major risk factor for osteoporotic fracture (OF). A large number of studies used BMD as the major surrogate phenotype for osteoporotic fracture. BMD is a quantitative trait determined by genetic and environmental factors, with heritability estimates ranging from 50% to 90%. Gender, age, height, weight, exercise, and hormone are also important factors related with BMD. The present study was performed to test the relation between gender, age, height, weight, some candidate genes and BMD at different skeletal sites in Chinese population. Our results showed as follows:1) The Spl and Rsal polymorphisms of the collagen type 1 alpha 1 (COL1 Al) 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 pi (TGF-P!) gene are absent or too rare in Chinese. Compared the polymorphisms of these five markers with other populations using %2 test and Fisher's exact two-tailed test, significant differences of allele and genotype frequency distributions were observed at these polymorphisms (p < 0.001).2) A significant difference of BMD among male-female groups (p < 0.003) was observed. After adjustment for weight using multiple regression analysis, the magnitude of sex difference of BMD was reduced at all studied skeletal sites; for example, the difference declines from 18.3% to 5.5% at spine. There were significant differences in BMD change among the age-stratified groups at all the sites in both sexes (p < 0.01), except spine BMD in males (p = 0.928). Regression analysis suggested that with aging, greater difference of BMD distribution exists inelderly females than males. Weight accounted for the greatest proportion of age-adjusted BMD variation (e.g., at femoral neck, R2 = 0.17 in males) among four variables: weight, height, BMI and a principal component formed from weight and height. The effect of height on BMD variation in elderly Chinese in our study may be mostly included in weight.3) We tested total-family association, within-family association (via TDT), and linkage, between the BsrBl marker and bone phenotypes (BMD and bone size) at the spine and the hip (femoral neck, torchanter and intertrochanter) in Chinese 402 nuclear families with a total number of 1263, and found the suggestive linkage (p - 0.037) between the IL-6 BsrBl maker and the Li₄ spine BMD. No significant association and linkage was found for bone size and hip BMD.The present studies represented molecular genetic research of bone mineral density, and identified some factors related to BMD in Chinese.