Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women

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Abstract

OBJECTIVE

We studied whether vitamin D receptor and estrogen receptor gene polymorphism is associated with the effect of hormone replacement therapy on lumbar-spinal bone mineral density in Japanese women.

STUDY DESIGN

The subjects were 82 Japanese women aged 40 to 64 years (49.7 +/- 0.6 years, mean +/- SEM) who had taken hormone replacement therapy for >1 year. Genomic deoxyribonucleic acid was extracted from blood and analyzed for restriction fragment length polymorphism with the restriction endonucleases TaqI, ApaI, and FokI for vitamin D receptor and PvuII and XbaI for estrogen receptor.

RESULTS

The subjects with genotype TT had a significantly higher percentage change in bone mineral density per year than those with the Tt genotype (2.8% +/- 0.6% vs -0.8% +/- 1.4%, P = .019). The serum level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen decreased by 13% during 1 year of hormone replacement therapy in subjects with the TT genotype (P = .001) but did not change in women with the Tt genotype. In multiple regression analysis including age, height (centimeters), weight (kilograms), and polymorphisms of the vitamin D receptor and estrogen receptor genes, only age and TaqI polymorphism of the vitamin D receptor gene were associated independently with change in bone mineral density (P = .001 and .004, respectively).

CONCLUSION

TaqI polymorphism of the vitamin D receptor gene is associated with the effect of hormone replacement therapy on lumbar-spinal bone mineral density and bone resorption markers in Japanese women. Analysis of the vitamin D receptor alleles may prove useful for selection of the optimum therapy for osteoporosis management. (Am J Obstet Gynecol 1999;180:1115-20.)

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