Yumiko Nagao1, Nao Nishida2, Licht Toyo-Oka3, Atsushi Kawaguchi4, Antonio Amoroso5, Marco Carrozzo6, Michio Sata7, Masashi Mizokami8, Katsushi Tokunaga3, Yasuhito Tanaka9. 1. 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. Electronic address: nagaoyu@cc.saga-u.ac.jp. 2. 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. 3. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. 4. Center for Comprehensive Community Medicine, Saga Medical School, Nabeshima, Saga, Japan. 5. Regional Transplantation Center, Piedmont, Molinette Hospital, AOU Citta della Salute e della Scienza di Torino, Turin, Italy. 6. Oral Medicine Department, Centre for Oral Health Research, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom. 7. Research Center for Innovative Cancer Therapy, Kurume University, Asahi-machi, Kurume, Japan; Nishinihon Hospital, Hattannda, Kumamoto, Japan. 8. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan. 9. Department of Virology, Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Abstract
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. METHODS: 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. RESULTS: Single-nucleotide polymorphisms in NRP2 (rs884000) and IGFBP4 (rs538399) were associated with risk of HCV-associated lichen planus (P < 1 × 10-4). 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. CONCLUSIONS: 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.
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. METHODS: 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-infectedpatients with normal oral mucosa treated at a medical center in Italy. RESULTS: Single-nucleotide polymorphisms in NRP2 (rs884000) and IGFBP4 (rs538399) were associated with risk of HCV-associated lichen planus (P < 1 × 10-4). 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. CONCLUSIONS: 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.
Authors: Brad T Sherman; Xiaojun Hu; Kanal Singh; Lillian Haine; Adam W Rupert; James D Neaton; Jens D Lundgren; Tomozumi Imamichi; Weizhong Chang; H Clifford Lane Journal: AIDS Date: 2021-02-02 Impact factor: 4.632