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Genetically predicted 17β-estradiol and systemic inflammation in women: a separate-sample Mendelian randomisation analysis in the Guangzhou Biobank Cohort Study
  1. J Zhao1,
  2. C Q Jiang2,
  3. T H Lam1,
  4. B Liu2,
  5. K K Cheng3,
  6. S Kavikondala1,
  7. W S Zhang2,
  8. G M Leung1,
  9. C M Schooling1,4
  1. 1School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR
  2. 2Guangzhou Number 12 Hospital, Guangzhou, China
  3. 3Department of Public Health and Epidemiology, University of Birmingham, UK
  4. 4CUNY School of Public Health and Hunter College, New York, USA
  1. Correspondence to Dr CM Schooling, G/F Patrick Manson Building (North Wing), 7 Sassoon Road, Hong Kong; cms1{at}


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 17β-estradiol with well-established systemic inflammatory markers (total white cell count, granulocyte and lymphocyte count).

Methods A genetic score predicting 17β-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 17β-estradiol with systemic inflammatory markers among 3096 older (50+ years) Chinese women from the Guangzhou Biobank Cohort Study.

Results Predicted 17β-estradiol was negatively associated with white blood cell count (−6.3 103/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 (−1.5 103/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 17β-estradiol reduced low-grade systemic inflammatory markers (white blood cell count and granulocyte count), consistent with experimental and ecological evidence of 17β-estradiol promoting immune response. Replication in a larger sample is required.

  • Epidemiology of Chronic Non Communicable Diseases
  • Life Course Epidemiology
  • Hormones

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