HFE p.C282Y /（纯合）基因型和中心性肥胖都会增加肝病和糖尿病的风险，但综合影响尚不清楚。我们估计了英国生物银行社区队列中 p.C282Y / 参与者的腰臀比 (WHR) 与常规护理中事件临床结果的关联。1,297 名男性和 1,602 名女性 p.C282Y / 的基线 WHR 平均随访时间为 13.3 年进行诊断。样条回归和 Cox 比例风险模型根据年龄和遗传主成分进行了调整。累积发病年龄为40岁至80岁。在 p.C282Y / 男性中，住院诊断的肝纤维化/肝硬化 (p=2.4*10-5)、肝癌 (p=0.007)、非酒精性脂肪性肝病 (NAFLD) (p=2.4*10-5) 之间存在正线性 WHR 关系=7.7*10-11) 和 2 型糖尿病 (T2D) (p=5.1*10-16)。 p.C282Y / 男性中高 WHR 的风险比 (HR) (≥0.96; 33.9%) 肝纤维化/肝硬化的风险比 (HR) = 4.13 (95% CI: 2.04-8.39, p=8.4*10-5 与正常相比腰臀比）； 80 岁累计发病率为 15.0% (95%CI: 9.8%-22.6%) 对比 3.9% (95%CI: 1.9%-7.6%)；肝癌的累积发病率为 9.2% (95%CI: 5.7%-14.6%) 和 3.6% (95%CI: 1.9%-6.6%)。在 24 名高 WHR p.C282Y / 患有纤维化/肝硬化的男性中，有 23 名 (96%) 被诊断为血色素沉着症。高腰臀比 (≥0.85; 30.0%) p.C282Y / 女性增加了肝纤维化/肝硬化 (HR=9.17, 95%CI: 2.51-33.50, p=3.8*10-7) 和 NAFLD (HR=5.17, 95%CI：2.48-10.78，p=1.2*10-5)。在具有额外初级保健诊断的子集中，纤维化/肝硬化的相关性相似。在 p.C282Y / 男性和女性中，腰臀比增加与肝脏并发症的风险显着升高相关。应测试减少中心性肥胖以改善这些结果的干预措施。版权所有 © 2024 作者。由 Wolters Kluwer Health, Inc. 出版

The HFE p.C282Y+/+ (homozygous) genotype and central adiposity both increase liver disease and diabetes risks, but combined effects are unclear. We estimated waist-to-hip ratio (WHR) associations with incident clinical outcomes in routine care in p.C282Y+/+ participants in the UK Biobank community cohort.Baseline WHR in 1,297 male and 1,602 female p.C282Y+/+ with 13.3-year mean follow-up for diagnoses. Spline regressions and Cox proportional hazard models were adjusted for age and genetic principal components. Cumulative incidence was from age 40 to 80 years. In p.C282Y+/+ males, there were positive linear WHR relationships for hospital inpatient diagnosed liver fibrosis/cirrhosis (p=2.4*10-5), liver cancer (p=0.007), non-alcoholic fatty liver disease (NAFLD) (p=7.7*10-11), and type 2 diabetes (T2D) (p=5.1*10-16). The Hazard Ratio (HR) for high WHR in p.C282Y+/+ males (≥0.96; 33.9%) was HR=4.13 for liver fibrosis/cirrhosis (95%CI: 2.04-8.39, p=8.4*10-5 vs. normal WHR); cumulative age 80 incidence 15.0% (95%CI: 9.8%-22.6%) versus 3.9% (95%CI: 1.9%-7.6%); for liver cancer, cumulative incidence was 9.2% (95%CI: 5.7%-14.6%) versus 3.6% (95%CI: 1.9%-6.6%). Hemochromatosis was diagnosed in 23 (96%) of the 24 high WHR p.C282Y+/+ males with incident fibrosis/cirrhosis. High WHR (≥0.85; 30.0%) p.C282Y+/+ females had raised hazards for liver fibrosis/cirrhosis (HR=9.17, 95%CI: 2.51-33.50, p=3.8*10-7) and NAFLD (HR=5.17, 95%CI: 2.48-10.78, p=1.2*10-5). Fibrosis/cirrhosis associations were similar in the subset with additional primary care diagnoses.In p.C282Y+/+ males and females, increasing WHR is associated with substantially higher risks of liver complications. Interventions to reduce central adiposity to improve these outcomes should be tested.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.