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The age-related decline of dehydroepiandrosterone sulphate levels is believed to contribute to the development of osteoporosis. We hypothesized that CYP3A7*1C may lead to bone loss through decreased levels of dehydroepiandrosterone sulphate in postmenopausal women. PATIENTS AND METHODS: 319 postmenopausal women were studied and divided into two subgroups: 217 women with osteoporosis and 102 aged-matched women without osteoporosis. The CYP3A7*1C polymorphism was genotyped. Serum dehydroepiandrosterone sulphate levels and bone mineral density were measured. RESULTS: Homozygous CYP3A7*1C carriers had significantly lower bone mineral density at lumbar spine than that of wild type (T-score with CYP3A7*1C mutant type: -3.27 +/- 1.02, T-score with wild type: -1.35 +/- 1.53, p = 0.041) after adjusting for age and DHEAS levels. No association was found between genotypes and dehydroepiandrosterone sulphate levels. 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