title: Genetically predicted 17β-estradiol and systemic inflammation in women: a separate-sample Mendelian randomisation analysis in the Guangzhou Biobank Cohort Study.
abstract: 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 10(3)/mL, 95% CI -11.4 to -1.3) and granulocyte count (-4.5 10(3)/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 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.
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Guangzhou Number 12 Hospital, Guangzhou, China.
authors.forename: C Q
authors.initials: CQ
authors.lastname: Jiang
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
authors.forename: T H
authors.initials: TH
authors.lastname: Lam
authors.affiliation: Guangzhou Number 12 Hospital, Guangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Public Health and Epidemiology, University of Birmingham, UK.
authors.forename: K K
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
authors.forename: S
authors.initials: S
authors.lastname: Kavikondala
authors.affiliation: Guangzhou Number 12 Hospital, Guangzhou, China.
authors.forename: W S
authors.initials: WS
authors.lastname: Zhang
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
authors.forename: G M
authors.initials: GM
authors.lastname: Leung
authors.affiliation: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR CUNY School of Public Health and Hunter College, New York, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Schooling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016001:Confidence Intervals; D004958:Estradiol / Q000097:blood / Q000235:genetics*; D005260:Female; D006098:Granulocytes; D006723:Hong Kong; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D007958:Leukocyte Count; D057182:Mendelian Randomization Analysis; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D004958:Estradiol
keywords: Epidemiology of Chronic Non Communicable Diseases; Hormones; Life Course Epidemiology