JOURNAL ARTICLE

The association of bone mineral density with estrogen receptor gene polymorphisms

Gail A Greendale, Jian Chu, Robert Ferrell, John F Randolph, Janet M Johnston, MaryFran R Sowers
American Journal of Medicine 2006, 119 (9 Suppl 1): S79-86
16949392
The purpose of this investigation was to evaluate single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and bone mineral density (BMD) of the lumbar spine (LS-BMD) or total hip (hip BMD) in women of 4 races/ethnicities who were premenopausal or in early perimenopause. The sample consisted of 1,301 participants from the Study of Women's Health Across the Nation (SWAN) with measures of BMD and genotyping; of these, 295 were African American, 693 were Caucasian, 151 were Chinese, and 162 were Japanese. We evaluated the potential association of LS-BMD or hip BMD with 4 SNPs from the ESR1 gene (ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 SNPs from the ESR2 gene (ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Unadjusted mean LS-BMD values ranged from 1.141+/-0.14 g/cm(2) in African American women to 1.031+/-0.11 g/cm2 in Japanese women; unadjusted mean hip BMD values ranged from 1.053+/-0.14 g/cm2 in African American women to 0.862+/-0.10 g/cm2 in Chinese women. African American and Japanese women with the ESR1 rs2234693 (PvuII) CC genotype had higher LS-BMDs than did their peers with the TT genotype (P=0.009 and P=0.04, respectively). Japanese women with the ESR1 rs3798577 CC or TC genotypes had lower LS-BMD than did Japanese women with the TT genotype (P=0.02 and P=0.01, respectively). Caucasian women with the TC genotype for ESR2 rs1256030 had lower LS-BMDs than did those with the CC genotype (P=0.02). Chinese women who were heterozygous for ESR2 rs1256030 or ESR2 rs1256065 had significantly higher LS-BMDs and hip BMDs than did the referent groups for each of these SNPs (CC and AA, respectively). Associations between BMD and ESR1 and ESR2 genotypes varied by race/ethnicity and by bone site. Our results differ from those previously reported for 2 ESR1 genotypes (ESR1 rs2234693 [PvuII] and ESR1 rs9340799 [XbaI]). Moreover, 2 ESR1 and 3 ESR2 SNPs we studied have not previously been examined with respect to BMD. Among these, ESR2 rs1256030 and ESR2 rs1256065 appear to have an effect at both the lumbar spine and hip in Chinese women and may warrant further study.

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