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Lookup NU author(s): Dr David Woods
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A reduction in interleukin-6 (IL-6) activity may contribute to the beneficial effects of hormone replacement therapy (HRT) on the menopausal decline in bone mineral density (BMD). We have examined this hypothesis using a genetic strategy. The -174C (rather than G) IL-6 gene variant is associated with lower IL-6 expression. As such, we might anticipate the C allele to be associated with a greater response to HRT. We have tested this hypothesis. Mean three-site [spine (L1-L4), neck of femur, and Ward's triangle] BMD was measured in 65 women in a 1-year randomised controlled trial of HRT with 0.625 mg oestrogen/day and 0.15 mg norgestrel (n=30). Baseline BMD was genotype-independent for both the control and HRT group. In the control group, the percentage change in BMD after 1 year was similar between genotypes (P=0.45). In contrast, in the HRT group, the rise was genotype-dependent. Those homozygous for the G allele showed a 3.62 (2.14)% increase in BMD compared with 10.44 (4.68)% for the C-homozygous group. Heterozygotes had an intermediate BMD increase of 5.6 (2.82)% [P=0.006 (P value for interaction between HRT and genotype was 0.04)] Although the study was limited by its small sample size, these are the first data to demonstrate the importance of IL-6 genotype in determining response to oestrogen therapy, rather than its physiological withdrawal.
Author(s): James L, Onambele G, Woledge R, Skelton D, Woods D, Eleftheriou K, Hawe E, Humphries SE, Haddad F, Montgomery H
Publication type: Article
Publication status: Published
Journal: European Journal of Applied Physiology
Year: 2004
Volume: 92
Issue: 1-2
Pages: 227-230
ISSN (print): 1439-6319
ISSN (electronic): 1439-6327
Publisher: Springer
URL: http://dx.doi.org/10.1007/s00421-004-1092-7
DOI: 10.1007/s00421-004-1092-7
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