Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China.
Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, 250021, China; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, China.
Dig Liver Dis. 2023 Aug;55(8):1091-1097. doi: 10.1016/j.dld.2023.02.020. Epub 2023 Mar 13.
Primary biliary cholangitis (PBC) primarily affects female in their 4th to 6th decade of life at which stage female's sex hormones change dramatically. Sex hormones have a wide range of effects on the liver and immune system. However, it remains unclear whether sex hormonal changes mediate the onset of PBC.
This study investigated the causal effect between total testosterone (TT), bioavailable testosterone (BAT), sex hormone binding globulin (SHBG) in female and PBC using public GWAS summary data.
Data on TT, BAT, SHBG in female were obtained from a previous study based on the UK Biobank. PBC GWAS summary data was obtained from a genome-wide meta-analysis. We used several methods to make the conclusion robust. Various sensitivity analyses had been conducted to assess the consistency of our findings.
Our Mendelian randomization analysis revealed that the genetically predicted BAT in female was positively associated with PBC and SHBG in female was negatively associated with PBC. The results obtained from different methods are similar, which proves the reliability of the results.
Our study supported a causal relationship of BAT and SHBG in female on PBC. To confirm the association between testosterone and PBC, more research should be conducted.
原发性胆汁性胆管炎（PBC）主要影响 40 至 60 岁的女性，在这个阶段女性的性激素会发生剧烈变化。性激素对肝脏和免疫系统有广泛的影响。然而，目前尚不清楚性激素变化是否介导 PBC 的发生。
本研究使用公共 GWAS 汇总数据，调查女性总睾酮（TT）、生物可利用睾酮（BAT）和性激素结合球蛋白（SHBG）与 PBC 之间的因果关系。
女性 TT、BAT、SHBG 的数据来自 UK Biobank 中的一项先前研究。PBC GWAS 汇总数据来自全基因组荟萃分析。我们使用了几种方法来使结论更可靠。进行了各种敏感性分析以评估我们研究结果的一致性。
我们的孟德尔随机化分析表明，女性中遗传预测的 BAT 与 PBC 呈正相关，而女性中 SHBG 与 PBC 呈负相关。不同方法得到的结果相似，这证明了结果的可靠性。
我们的研究支持女性 BAT 和 SHBG 与 PBC 之间存在因果关系。为了确认睾酮与 PBC 之间的关联，需要进行更多的研究。
