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  • Title: Association of a -1997G-->T polymorphism of the collagen Ialpha1 gene with bone mineral density in postmenopausal Japanese women.
    Author: Yamada Y, Ando F, Niino N, Shimokata H.
    Journal: Hum Biol; 2005 Feb; 77(1):27-36. PubMed ID: 16114814.
    Abstract:
    Genetic variants that affect collagen Ialpha1 metabolism may be important in the development of osteoporosis or osteoporotic fractures. A -1997G-->T polymorphism in the promoter of the collagen Ialpha1 gene (COL1A1) was shown to be associated with bone mineral density (BMD) for the lumbar spine in postmenopausal Spanish women. The relation of this polymorphism to BMD in Japanese women or men has now been examined in a population-based study. The subjects (1,110 women, 1,126 men) were 40 to 79 years of age and were randomly recruited for a population-based prospective cohort study of aging and age-related diseases. BMD for the lumbar spine, right femoral neck, right trochanter, and right Ward's triangle was measured using dual-energy x-ray absorptiometry. Genotypes for the -1997G-->T polymorphism of COL1A1 were determined with a fluorescence-based allele-specific DNA primer assay system. When all women were analyzed together, BMD for the lumbar spine and trochanter was significantly lower in subjects with the COL1A1 *G/*G genotype than in those in the combined group of COL1A1 *G/*T and COL1A1 *T/*T genotypes. When postmenopausal women were analyzed separately, BMD for the femoral neck and trochanter was also significantly lower in those with the COL1A1 *G/*G genotype than in those with the COL1A1 *G/*T genotype or those in the combined group of COL1A1*G/*T and COL1A1 *T/*T genotypes. BMD was not associated with -1997G-->T genotype in premenopausal women or in men. Multivariate regression analysis revealed that -1997G-->T genotype affected BMD at various sites with a variance of 0.46-0.62% for all women and 0.61-1.01% for postmenopausal women. The -1997G-->T genotype was not related to the serum concentration of osteocalcin, the serum activity of bone-specific alkaline phosphatase, or the urinary excretion of deoxypyridinoline or cross-linked N-telopeptides of type I collagen in men or in premenopausal or postmenopausal women. These results suggest that COL1A1 is a susceptibility locus for reduced BMD in postmenopausal Japanese women.
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