title: Genome-Wide Association Study Identifies Risk Variants for Lichen Planus in Patients With Hepatitis C Virus Infection.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nagao
authors.affiliation: 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.
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Licht
authors.initials: L
authors.lastname: Toyo-Oka
authors.affiliation: Center for Comprehensive Community Medicine, Saga Medical School, Nabeshima, Saga, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Regional Transplantation Center, Piedmont, Molinette Hospital, AOU Citta della Salute e della Scienza di Torino, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.affiliation: Oral Medicine Department, Centre for Oral Health Research, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Carrozzo
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Asahi-machi, Kurume, Japan; Nishinihon Hospital, Hattannda, Kumamoto, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Department of Virology, Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics*; D007564:Japan; D008010:Lichen Planus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D039943:Neuropilin-2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D062606:Tertiary Care Centers
chemical_list: D018974:Insulin-Like Growth Factor Binding Protein 4; D039943:Neuropilin-2; C581308:neuropilin-2, human
keywords: Autoimmunity; Inflammation; Oral Mucosa; Risk Factor