J Korean Soc Endocrinol.
1996 Dec;11(4):468-478.
Estrogen Receptor Gene Polymorphism, Urinary Estrogen Metabolites and Bone Mineral Density in Korean Postmenopausal Women
Abstract
- Background
Estrogen status is important for maintaining the homeostasis of bone. Estrogen has direct effects on bone cells, through binding to the high-affinity estrogen receptor. Several recent studies suggest that there might be genetically determined variations in biosynthesis and function of estrogen receptor in postmenopausal osteoporosis. Also the main cause of postmenopausal osteoporosis is decreased level of serum estrogen, whereas there had been some suggestion that the remaining estrogen have some effect on bone metabolism after menopause. We investigated the relationship between estrogen receptor gene PvulI polymorphism and bone mineral density(BMD), and the relationship between 18 urinary metabolites of estrogen and BMD in Korean postmeno- pausal osteoporosis. Methods: We examined the PvuII polymorphism of the estrogen receptor gene in 5' upstream region and the first intron by restrietion frapnent length polymorphism analysis in 62 postmeno- pausal wornen, BMD was measured by DEXA. The urinary estrogen metabolites were determined by GC/MS(Gas Chromatography-Mass Spectrometry) at Korean Institute of Science and Techno- logy Doping Control Center. Results: BMD of the spine and the femoral neck correlated with body weight, height, body mass index as we expected. There was no polymorphism of PvuII restriction site on 5 upstream region of estrogen receptor gene. Whereas the prevalen~ee of the PP, Pp, pp genotype in the first intron of estrogen receptor was 12.9%, 45.2%, 41.9%, respectively. But, there was no correlation between PvuII genotype and the spinel and femoral neck BMD. 2(OH)E2 among 18 urinary metabolites of estrogen, showed a negative correlation with the spinal and femoral neck BMD(r =-0.2551, p<0.05, and r =-0.3341, p<0.01, respectively), and the ratio of 16a(OH)E2/2(OH)E1> revealed a positive correlation with the spinal BMD(r =0.3057, p<0.05). In stepwise multiple regression analysis, body weight, 2(OH)E2, 16a(OH)E1, 2(Meo)E1 were independent predictors of the spinal bone density, and body weight and 2(OH)E2 were independent predictors of the femoral neck bone density. Conclusion: These results suggested that restrietion fragment length polymorphism analysis of the estrogen receptor gene with PvuII restriction enzyme was not helpful for early detection of patients at risk of developing osteoporosis. However, the ratio of 16-hydroxylation to 2-hydroxylation of estrogen metabolism was reduced in postmenopausal women and high catecholestrogen formation might be a greater risk factor for osteoporosis.
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