, Volume 74, Issue 6, pp 501-508
Date: 17 Feb 2004

Estrogen Receptor β Dinucleotide (CA) Repeat Polymorphism is Significantly Associated with Bone Mineral Density in Postmenopausal Women

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Significant associations between the lengths of a highly polymorphic dinucleotide (CA) repeat located within the human estrogen receptor beta (ESR2) gene on chromosome 14, bone mineral density (BMD) and androgen levels have been reported previously in premenopausal women. We measured the size of this microsatellite repeat in 226 healthy women (60–98 years). After adjustment for age, body mass index, hormone replacement status, and other variables known to influence BMD, women with <25 CA repeats had significantly higher BMD measured in the total skeleton, lumbar spine, and femoral neck when compared with women having longer alleles. Women with shorter alleles also had higher circulating estrone and estradiol levels that approached statistical significance as compared with women harboring longer alleles after appropriate adjustments were performed in linear regression models. Women having both short and long CA repeats had BMD values in all regions of the skeleton that were midway between those found in women homozygous for longer or shorter repeat sizes. Because the ESR2 CA repeat size was neither associated with change in BMD nor serum levels of biochemical markers of bone turnover, it is likely that ESR2 CA repeat genotype is significantly linked to the attainment of peak bone mass in women.

This work was supported by grants AG10149 and AG02049 from the National Institutes of Health.