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Cai, X. ; Thorand, B. ; Hohenester, S.* ; Prehn, C. ; Cecil, A. ; Adamski, J. ; Zeller, T.* ; Dennis, A.* ; Banerjee, R.* ; Peters, A. ; Yaghootkar, H.* ; Nano, J.

Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: An observational and Mendelian randomization study.

Front. Endocrin. 14:1223162 (2023)

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BACKGROUND: Sex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous sex hormones, including testosterone (T), and SHBG with liver fat using complementary observational and Mendelian randomization (MR) analyses. METHODS: The observational analysis included a total of 2,239 participants (mean age 60 years; 35% postmenopausal women) from the population-based KORA study (average follow-up time: 6.5 years). We conducted linear regression analysis to investigate the sex-specific associations of sex hormones and SHBG with liver fat, estimated by fatty liver index (FLI). For MR analyses, we selected genetic variants associated with sex hormones and SHBG and extracted their associations with magnetic resonance imaging measured liver fat from the largest up to date European genome-wide associations studies. RESULTS: In the observational analysis, T, dihydrotestosterone (DHT), progesterone and 17α-hydroxyprogesterone (17-OHP) were inversely associated with FLI in men, with beta estimates ranging from -4.23 to -2.30 [p-value <0.001 to 0.003]. Whereas in women, a positive association of free T with FLI (β = 4.17, 95%CI: 1.35, 6.98) was observed. SHBG was inversely associated with FLI across sexes [men: -3.45 (-5.13, -1.78); women: -9.23 (-12.19, -6.28)]. No causal association was found between genetically determined sex hormones and liver fat, but higher genetically determined SHBG was associated with lower liver fat in women (β = -0.36, 95% CI: -0.61, -0.12). CONCLUSION: Our results provide suggestive evidence for a causal association between SHBG and liver fat in women, implicating the protective role of SHBG against liver fat accumulation.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords European Cohort ; Mendelian Randomization ; Fatty Liver Index ; Liver Fat ; Sex Hormone-binding Globulin ; Sex Hormones; Hepatic Steatosis; Genome-wide; Testosterone; Population; Kora; Dehydroepiandrosterone; Disease; Obese; Risk; Dhea

ISSN (print) / ISBN 1664-2392

e-ISSN 1664-2392

Journal Frontiers in Endocrinology

Quellenangaben Volume: 14, Article Number: 1223162

Publisher Frontiers

Publishing Place Lausanne

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Experimental Genetics (IEG)

Grants German Ministry of Education and Research (BMBF)
German Centre for Cardiovascular Research (DZHK)
EU
German Research Foundation
State of Bavaria
Helmholtz Zentrum Munchen, German Research Center for Environmental Health (GmbH) - German Federal Ministry of Education and Research (BMBF)