IL-6–174G/C genotype is associated with the bone mineral density response to oestrogen replacement therapy in post-menopausal women
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.
KeywordsInterleukin-6 Polymorphism Bone remodelling Hormone replacement therapy Bone mineral density
The original core study was funded by an educational grant from Wyeth Lederle. L.J. is funded as a research fellow by the charity Research into Ageing, UK. H.M. is funded by the Portex Endowment at the institute of Child health, London. The British Heart Foundation core funds The Centre for Cardiovascular Genetics, UCL. O.N.G.L. was funded by the Conquest Hospital in Hastings. The study received ethical approval from the UCL & UCH Ethics Committee in full compliance with the current U.K. laws. Written informed consent was obtained from all participants.
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