IngentaConnect Oestrogen-receptor- gene polymorphism affects response in bone mi...

Abstract:

OBJECTIVE

An oestrogen-receptor-α (ERα) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERα gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post-menopausal women in relation to ERα gene polymorphism. PATIENTS AND MEASUREMENTS

Subjects consisted of 124 Thai post-menopausal women. Sixty-three of the women were less than 6 years post-menopausal and 61 were more than 10 years post-menopausal with vertebral or femoral osteoporosis as defined by BMD T-score less than − 2.5. Subjects were randomly allocated to receive 0.3 mg (n = 67) or 0.625 mg (n = 57) of conjugated equine oestrogen (CEE). All subjects also took 5 mg medroxyprogesterone acetate. Vertebral and femoral neck BMD were measured at baseline and 1 year after treatment. Data were expressed as mean ± SEM. Capital P represents the absence of the restriction site while lower-case p indicates the presence of the restriction site. RESULTS

For subjects on 0.625 mg CEE, BMD at L2-4 increased significantly after 1 year in those with pp (n = 20) Pp (n = 29) and PP genotypes (n = 8) (P < 0.001). However, in subjects on 0.3 mg CEE, BMD at L2-4 increased significantly after 1 year in subjects with Pp (n = 34, + 7.6 ± 1.5%, P < 0.001) and PP genotypes (n = 13, + 6.9 ± 1.0%, P < 0.001), but not in those with pp genotype (n = 20, + 2.3 ± 2.1%, P = NS). After adjusting for age and years since menopause, the change in vertebral BMD was still lower in those without the P allele compared to those with the P allele (P < 0.05). Femoral BMD did not significantly change regardless of dose of CEE and genotype. CONCLUSIONS

We conclude that ERα gene polymorphism affects skeletal response to oestrogen in post-menopausal women. The effect of ERα gene polymorphism appears to be site-specific and does not relate to biochemical markers of bone turnover. Determination of ERα genotype may help identify post-menopausal women who will have more skeletal benefit from oestrogen therapy.

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Oestrogen-receptor-α gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women