Association of IFNL3 and IFNL4 polymorphisms with liver-related mortality in a multiracial cohort of HIV/HCV-coinfected women.
Association of IFNL3 and IFNL4 polymorphisms with liver-related mortality in a multiracial cohort of HIV/HCV-coinfected women.
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DOI：
10.1111/jvh.12431
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发表时间：
2015-12
影响因子：
2.5
通讯作者：
Women's Interagency HIV
中科院分区：
文献类型：
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作者：
Sarkar M;Aouzierat B;Bacchetti P;Prokunina-Olsson L;French A;Seaberg E;O'Brien TR;Kuniholm MH;Minkoff H;Plankey M;Strickler HD;Peters MG;Women's Interagency HIV
非洲裔美国人同时感染艾滋病毒和丙型肝炎病毒 (HCV) 的肝脏相关死亡率低于白人和西班牙裔。虽然 IFNL3 和 IFNL4 基因附近的遗传多态性解释了几种 HCV 相关结果中很大一部分种族差异，但这些变异对肝脏相关死亡率的影响尚未得到研究。我们对同时感染 HIV/HCV 的女性进行了一项队列研究，该研究是在 NIH 资助的多中心女性机构间 HIV 研究 (WIHS) 中进行的，旨在通过显性、隐性或加性遗传模型研究跨越 IFN-λ 区域的 10 个多态性是否与肝脏相关死亡率相关。我们还考虑了这些多态性是否导致了先前报道的按种族/族裔划分的肝脏相关死亡差异（通过自我报告和祖先信息标记确定）。在长达 18 年的随访中，794 名合并感染的女性中有 471 人死亡，其中 55 人死于肝脏相关疾病。经过调整分析，rs12980275 GG 基因型与 AG+AA 相比的风险比 [(HR) 0.36，95% CI 0.14–0.90，P = 0.029] 和 rs8109886 AA 基因型与 CC+AC 相比（HR 0.67，95% CI 0.45–0.99，P = 0.047）与肝脏相关死亡的相关性最强，尽管在调整种族/民族后这些相关性不再显着（HR 0.41，95% CI 0.16-1.04，P = 0.060；HR 0.78，95% CI 0.51-1.19，P = 0.25）。非洲裔美国女性的肝脏相关死亡率持续较低，与 IFN-λ 变异无关（HR ≤ 0.44，P 值 ≤ 0.04）。非裔美国 HIV/HCV 合并感染女性的较低死亡风险不能用 IFN-λ 区域的遗传变异来解释，这表明其他遗传、行为和/或环境因素可能导致肝脏相关死亡率的种族/民族差异。
African Americans coinfected with HIV and hepatitis C virus (HCV) have lower liver-related mortality than Caucasians and Hispanics. While genetic polymorphisms near the IFNL3 and IFNL4 genes explain a significant fraction of racial differences in several HCV-related outcomes, the impact of these variants on liver-related mortality has not been investigated. We conducted a cohort study of HIV/HCV-coinfected women followed in the multicentre, NIH-funded Women’s Interagency HIV Study (WIHS) to investigate whether 10 polymorphisms spanning the IFN-λ region were associated with liver-related mortality by dominant, recessive or additive genetic models. We also considered whether these polymorphisms contributed to previously reported differences in liver-related death by race/ethnicity (ascertained by self-report and ancestry informative markers). Among 794 coinfected women, there were 471 deaths including 55 liver-related deaths during up to 18 years of follow-up. On adjusted analysis, rs12980275 GG genotype compared to AG+AA hazards ratios [(HR) 0.36, 95% CI 0.14–0.90, P = 0.029] and rs8109886 AA genotype compared to CC+AC (HR 0.67, 95% CI 0.45–0.99, P = 0.047) were most strongly associated with liver-related death although these associations were no longer significant after adjusting for race/ethnicity (HR 0.41, 95% CI 0.16–1.04, P = 0.060 and HR 0.78, 95% CI 0.51–1.19, P = 0.25, respectively). African American women had persistently lower liver-related death independent of IFN-λ variants (HRs ≤ 0.44, P values ≤ 0.04). The lower risk of death among African American HIV/HCV-coinfected women is not explained by genetic variation in the IFN-λ region suggesting, that other genetic, behavioural and/or environmental factors may contribute to racial/ethnic differences in liver-related mortality.