Journal
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
Volume 68, Issue 8, Pages 780-785Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jech-2013-203451
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Funding
- University of Hong Kong Foundation for Development and Research (Hong Kong, China)
- University of Hong Kong University Research Committee Strategic Research Theme of Public Health (Hong Kong, China)
- Guangzhou Public Health Bureau (Guangzhou, China)
- Guangzhou Science and Technology Bureau (Guangzhou, China)
- University of Birmingham (Birmingham, UK)
- Research Grant Council General Research Fund [769710]
- Research Grant Council of Hong Kong, Hong Kong SAR, People's Republic of China
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Background Many chronic diseases are characterised by low-grade systemic inflammation. Oestrogens may promote immune response consistent with sex-specific patterns of diseases. In vitro culture and animal experiments suggest oestrogens are anti-inflammatory and might thereby protect against low-grade systemic inflammation. Evidence from epidemiological studies is limited. Using a Mendelian randomisation analysis with a separate-sample instrumental variable (SSIV) estimator, we examined the association of genetically predicted 17 beta-estradiol with well-established systemic inflammatory markers (total white cell count, granulocyte and lymphocyte count). Methods A genetic score predicting 17 beta-estradiol was developed in 237 young Chinese women (university students) from Hong Kong based on a parsimonious set of genetic polymorphisms (ESR1 (rs2175898) and CYP19A1 (rs1008805)). Multivariable linear regression was used to examine the association of genetically predicted 17 beta-estradiol with systemic inflammatory markers among 3096 older (50+ years) Chinese women from the Guangzhou Biobank Cohort Study. Results Predicted 17 beta-estradiol was negatively associated with white blood cell count (-6.3 10(3)/mL, 95% CI -11.4 to -1.3) and granulocyte count (-4.5 103/mL, 95% CI -8.5 to -0.4) but not lymphocyte count (-1.5 10(3)/mL, 95% CI -3.4 to 0.4) adjusted for age only. Results were similar further adjusted for education, smoking, use of alcohol, physical activity, Body Mass Index, waist-hip ratio, age of menarche, age at menopause, use of hormonal contraceptives and hormone replacement therapy. Conclusions Endogenous genetically predicted 17 beta-estradiol reduced low-grade systemic inflammatory markers (white blood cell count and granulocyte count), consistent with experimental and ecological evidence of 17 beta-estradiol promoting immune response. Replication in a larger sample is required.
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