Liver international : official journal of the International Association for the Study of the Liver · 2024
Association of sex hormones with non-alcoholic fatty liver disease: An observational and Mendelian randomization study.
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Weng Chenghao, Shao Zilun, Xiao Meng, Song Mingyu, Zhao Yuxuan, Li Aolin, Pang Yuanjie, Huang Tao, Yu Canqing, Lv Jun, Li Liming, Sun Dianjianyi
Аннотация
BACKGROUND AND AIMS: Sex-specific associations of sex hormone-binding globulin (SHBG) and bioavailable testosterone (BAT) with NAFLD remain indeterminate. We aimed to explore observational and genetically determined relationships between each hormone and NAFLD.
METHODS: We included 187 395 men and 170 193 women from the UK Biobank. Linear and nonlinear Cox regression models and Mendelian randomization (MR) analysis were used to test the associations.
RESULTS: During 12.49 years of follow-up, 2209 male and 1886 female NAFLD cases were documented. Elevated SHBG levels were linearly associated with a lower risk of NAFLD in women (HR (95% CI), .71 (.63, .79)), but not in men (a "U" shape, pnon-linear < .001). Higher BAT levels were associated with a lower NAFLD risk in men (HR (95% CI), .81 (.71, .93)) but a higher risk in women (HR (95% CI): 1.25 (1.15, 1.36)). Genetically determined SHBG and BAT levels were linearly associated with NAFLD risk in women (OR (95% CI): .57 (.38, .87) and 2.21 (1.41, 3.26) respectively); in men, an "L-shaped" MR association between SHBG levels and NAFLD risk was found (pnon-linear = .016). The bidirectional MR analysis further revealed the effect of NAFLD on SHBG and BAT levels in both sexes.
CONCLUSIONS: Consistently, linear associations of lower SHBG and higher BAT levels with increased NAFLD risk were both conventionally and genetically found in women, while in men, SHBG acts in a nonlinear manner. In addition, NAFLD may affect SHBG and BAT levels.
METHODS: We included 187 395 men and 170 193 women from the UK Biobank. Linear and nonlinear Cox regression models and Mendelian randomization (MR) analysis were used to test the associations.
RESULTS: During 12.49 years of follow-up, 2209 male and 1886 female NAFLD cases were documented. Elevated SHBG levels were linearly associated with a lower risk of NAFLD in women (HR (95% CI), .71 (.63, .79)), but not in men (a "U" shape, pnon-linear < .001). Higher BAT levels were associated with a lower NAFLD risk in men (HR (95% CI), .81 (.71, .93)) but a higher risk in women (HR (95% CI): 1.25 (1.15, 1.36)). Genetically determined SHBG and BAT levels were linearly associated with NAFLD risk in women (OR (95% CI): .57 (.38, .87) and 2.21 (1.41, 3.26) respectively); in men, an "L-shaped" MR association between SHBG levels and NAFLD risk was found (pnon-linear = .016). The bidirectional MR analysis further revealed the effect of NAFLD on SHBG and BAT levels in both sexes.
CONCLUSIONS: Consistently, linear associations of lower SHBG and higher BAT levels with increased NAFLD risk were both conventionally and genetically found in women, while in men, SHBG acts in a nonlinear manner. In addition, NAFLD may affect SHBG and BAT levels.