Genetically Predicted Testosterone and Systemic Inflammation in Men: A Separate-Sample Mendelian Randomization Analysis in Older Chinese Men |
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Authors: | Jie Zhao Chaoqiang Jiang Tai Hing Lam Bin Liu Kar Keung Cheng Lin Xu Shiu Lun Au Yeung Weisen Zhang Gabriel M. Leung C. Mary Schooling |
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Affiliation: | 1School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China;2Guangzhou Number 12 Hospital, Guangzhou, China;3Department of Public Health and Epidemiology, University of Birmingham, Birmingham, United Kingdom;4School of Urban Public Health, Hunter College, CUNY School of Public Health, New York, New York, United States of America;University of Sydney, AUSTRALIA |
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Abstract: | ObjectivesObservationally, testosterone is negatively associated with systemic inflammation, but this association is open to both residual confounding and reverse causality. Large-scale randomized controlled trials (RCTs), assessing exogenous effects, are presently unavailable. We examined the association of endogenous testosterone with well-established systemic inflammatory markers (white blood cell, granulocyte, lymphocyte and high-sensitivity C-reactive protein (hsCRP)) using a separate-sample Mendelian randomization analysis to minimize reverse causality.MethodsA genetic prediction rule for serum testosterone was developed in 289 young Chinese men with mean age of 21.0, using selected testosterone-related SNPs (rs10046, rs1008805 and rs1256031). Multivariable linear regression was used to examine the association of genetically predicted serum testosterone with inflammatory markers among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study.ResultsGenetically predicted testosterone was unrelated to white blood cell count (-0.01 109/L per nmol/L testosterone, 95% confidence interval (CI) -0.05 to 0.04), granulocyte count (-0.02 109/L, 95% CI -0.06 to 0.02), lymphocyte count (0.005 109/L, 95% CI -0.01 to 0.02) and hsCRP (-0.05 mg/L, 95% CI -0.15 to 0.06).ConclusionOur findings did not corroborate any anti-inflammatory effects of testosterone or corresponding potentially protective effects of testosterone on chronic diseases resulting from reduced low-grade systemic inflammation. |
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