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Association of estrogen receptor alpha gene microsatellite polymorphism with annual changes in bone mineral density in Korean women with hormone replacement therapy

Cited 12 time in Web of Science Cited 17 time in Scopus
Authors
Yim, Chang Hoon; Choi, Jong Tae; Choi, Hyun Ah; Kang, Young Soon; Moon, In Gul; Yoon, Hyun Koo; Han, In Kwon; Kang, Dae Hee; Han, Ki Ok
Issue Date
2005-09-01
Publisher
Springer Verlag
Citation
J Bone Miner Metab. 2005;23(5):395-400.
Keywords
AdultAgedAllelesBone DensityBone and BonesDNA/metabolismEstrogen Receptor alpha/*genetics/metabolismFemaleFemur Neck/pathologyGenotypeHip/pathologyHormone Replacement TherapyHumansIntronsKoreaLumbar Vertebrae/metabolismMale*Microsatellite RepeatsMiddle AgedOsteoporosis, Postmenopausal/genetics*Polymorphism, Genetic
Abstract
Variation in drug response to hormone replacement therapy (HRT) may reflect genetic heterogeneity in the estrogen-related genes, possibly including estrogen receptor alpha (ERalpha) gene. However, only a few association studies of the drug response to HRT have been reported, focusing mainly on the intronic polymorphisms of the ERalpha gene. We therefore examined 284 postmenopausal women (mean age, 52.2 +/- 5.0 years) for the microsatellite thymine-adenine (TA) repeat polymorphism in the promoter of the ERalpha gene and its relationship to drug response by measuring changes in bone mineral density (BMD) after 1 year of HRT. In our study population, the most common number of TA repeats was 14, with a range of values between 11 and 27. At baseline, the number of TA repeats was neither associated with measured lumbar spine or femoral neck BMD nor with bone markers. When we categorized the subjects by the TA repeat numbers into an L group (n = 142), with a low mean number of repeats (TA < 16), and an H group (n = 142), with a high mean number of repeats (TA > or = 16), no significant genotypic differences were noted in spinal or femoral neck BMD or in bone markers. However, the drug response on lumbar spine BMD after 1 year of HRT correlated with the mean number of TA repeats (r = -0.131, P = 0.035) after adjustment for confounding factors such as body mass index and years since menopause. This correlation was also seen with the number of TA repeats on the shorter allele (r = -0.159, P = 0.012), which was defined as the allele with the lower number of TA repeats. However, this genotypic association was not found in the femoral neck BMD (r = 0.053, P = 0.396). When we defined the nonresponder group as women who had lost BMD even with HRT, 15.9% of the subjects were included, and this group was significantly younger and had higher initial BMD than the responder group. After further adjustment for age and initial BMD, the number of TA repeats on the shorter allele remained significantly associated with drug responsiveness (P = 0.005). These data indicate significant effects of the ERalpha TA repeat polymorphism on the estrogen responsiveness of lumbar spine BMD after 1 year of HRT in Korean women.
ISSN
0914-8779 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16133690

http://hdl.handle.net/10371/24595
DOI
https://doi.org/10.1007/s00774-005-0619-2
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College of Medicine/School of Medicine (의과대학/대학원)Preventive Medicine (예방의학전공)Journal Papers (저널논문_예방의학전공)
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