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.
James
L
L
Department of Orthopaedic Surgery, University College London NHS Trust, Mortimer Street, London, W1N 8AA, UK.
Onambele
G
G
Woledge
R
R
Skelton
D
D
Woods
D
D
Eleftheriou
K
K
Hawe
E
E
Humphries
S E
SE
Haddad
F
F
Montgomery
H
H
D015519:Bone Density / Q000187:drug effects* / Q000235:genetics; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000379:methods / Q000706:statistics & numerical data*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D009644:Norgestrel / Q000008:administration & dosage*; D015663:Osteoporosis, Postmenopausal / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*; D017698:Postmenopause / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
D004967:Estrogens; D015850:Interleukin-6; D009644:Norgestrel