Department of Organ System Interactions and Information, Saga Medical School, Nabeshima, Saga, Japan; Research Center for Innovative Cancer Therapy, Kurume University, Asahi-machi, Kurume, Japan.
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Clin Gastroenterol Hepatol. 2017 Jun;15(6):937-944.e5. doi: 10.1016/j.cgh.2016.12.029. Epub 2017 Jan 5.
BACKGROUND & AIMS: There is a close relationship between hepatitis C virus (HCV) infection and lichen planus, a chronic inflammatory mucocutaneous disease. We performed a genome-wide association study (GWAS) to identify genetic variants associated with HCV-related lichen planus.
We conducted a GWAS of 261 patients with HCV infection treated at a tertiary medical center in Japan from October 2007 through January 2013; a total of 71 had lichen planus and 190 had normal oral mucosa. We validated our findings in a GWAS of 38 patients with HCV-associated lichen planus and 7 HCV-infected patients with normal oral mucosa treated at a medical center in Italy.
Single-nucleotide polymorphisms in NRP2 (rs884000) and IGFBP4 (rs538399) were associated with risk of HCV-associated lichen planus (P < 1 × 10). We also found an association between a single-nucleotide polymorphism in the HLA-DR/DQ genes (rs9461799) and susceptibility to HCV-associated lichen planus. The odds ratios for the minor alleles of rs884000, rs538399, and rs9461799 were 3.25 (95% confidence interval, 1.95-5.41), 0.40 (95% confidence interval, 0.25-0.63), and 2.15 (95% confidence interval, 1.41-3.28), respectively.
In a GWAS of Japanese patients with HCV infection, we replicated associations between previously reported polymorphisms in HLA class II genes and risk for lichen planus. We also identified single-nucleotide polymorphisms in NRP2 and IGFBP4 loci that increase and reduce risk of lichen planus, respectively. These genetic variants might be used to identify patients with HCV infection who are at risk for lichen planus.
丙型肝炎病毒（HCV）感染与扁平苔藓密切相关，扁平苔藓是一种慢性炎症性黏膜疾病。我们进行了全基因组关联研究（GWAS），以鉴定与 HCV 相关的扁平苔藓相关的遗传变异。
我们对 2007 年 10 月至 2013 年 1 月在日本一家三级医疗中心接受治疗的 261 例 HCV 感染患者进行了 GWAS；共有 71 例患有扁平苔藓，190 例口腔黏膜正常。我们在意大利一家医疗中心接受治疗的 38 例 HCV 相关扁平苔藓患者和 7 例 HCV 感染患者的 GWAS 中验证了我们的发现。
NRP2（rs884000）和 IGFBP4（rs538399）中的单核苷酸多态性与 HCV 相关扁平苔藓的风险相关（P < 1×10）。我们还发现 HLA-DR/DQ 基因中的单核苷酸多态性（rs9461799）与 HCV 相关扁平苔藓的易感性之间存在关联。rs884000、rs538399 和 rs9461799 的次要等位基因的优势比分别为 3.25（95%置信区间，1.95-5.41）、0.40（95%置信区间，0.25-0.63）和 2.15（95%置信区间，1.41-3.28）。
在对日本 HCV 感染患者的 GWAS 中，我们复制了先前报道的 HLA Ⅱ类基因多态性与扁平苔藓风险之间的关联。我们还鉴定了 NRP2 和 IGFBP4 基因座中的单核苷酸多态性，它们分别增加和降低扁平苔藓的风险。这些遗传变异可能用于识别 HCV 感染患者中患有扁平苔藓的风险。
