Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Hepatology. 2010 May;51(5):1514-22. doi: 10.1002/hep.23515.
Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB10101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1-2.6), B5701 (PR=2.0; 95% CI = 1.0-3.1), B5703 (PR = 1.7; 95% CI = 1.0-2.5), and Cw0102 (PR = 1.9; 95% CI = 1.0-3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB10301 (PR = 0.4; 95% CI = 0.2-0.7) was associated with HCV RNA positivity. DQB10301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2-11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed.
HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized.
对人类白细胞抗原 (HLA) 等位基因及其与丙型肝炎病毒 (HCV) 病毒血症的关系的研究结果存在争议。然而,这些研究在规模和方法上存在差异,并且很少有大型研究评估 HLA Ⅰ类等位基因。只有一项研究进行了 HLA Ⅰ类高分辨率基因分型。因此,目前的研究涉及对美国 HCV 和 HIV 感染率高的大型多种族女性队列进行 HLA Ⅰ类和Ⅱ类高分辨率基因分型。我们的主要分析评估了通过文献综述确定的 12 个 HLA 等位基因与 758 名 HCV 血清阳性女性 HCV 病毒血症之间的关联。还评估了其他流行率>5%的等位基因;对以前未报告的关联进行了多次比较校正。DRB10101(优势比 [PR] = 1.7;95%置信区间 [CI] = 1.1-2.6)、B5701(PR=2.0;95%CI = 1.0-3.1)、B5703(PR = 1.7;95% CI = 1.0-2.5)和 Cw0102(PR = 1.9;95% CI = 1.0-3.0)与 HCV RNA 缺失(即 HCV 清除)相关,而 DRB10301(PR = 0.4;95% CI = 0.2-0.7)与 HCV RNA 阳性相关。DQB10301 也与 HCV RNA 缺失相关,但仅在 HIV 血清阴性女性中(PR = 3.4;95% CI = 1.2-11.8)。这些关联均在预测范围内。我们还研究了 HLA 等位基因与来自注射吸毒的 HCV 高危女性(N = 838)的 HCV 感染(血清状态)之间的关系,但未观察到显著关系。
HLA 基因型影响宿主清除 HCV 病毒血症的能力。当前研究中观察到的特定 HLA 关联不太可能是偶然的,因为它们是先验假设的。