James, L and Onambele, G and Woledge, R and Skelton, D and Woods, D and Eleftheriou, K and Hawe, E and Humphries, SE and Haddad, F and Montgomery, H (2004) IL-6-174G/C genotype is associated with the bone mineral density response to oestrogen replacement therapy in post-menopausal women. EUR J APPL PHYSIOL , 92 (1-2) 227 - 230. 10.1007/s00421-004-1092-7.
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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.
|Title:||IL-6-174G/C genotype is associated with the bone mineral density response to oestrogen replacement therapy in post-menopausal women|
|Keywords:||interleukin-6, polymorphism, bone remodelling, hormone replacement therapy, bone mineral density, INTERLEUKIN-6, GENE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Clinical Physiology|
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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