title: Association of a single nucleotide polymorphism upstream of ICOS with Japanese autoimmune hepatitis type 1.
abstract: Autoimmune hepatitis (AIH) is an uncommon chronic autoimmune liver disease. Several studies reported the association of polymorphisms between CD28, CTLA4 and ICOS gene cluster in 2q33.2 with autoimmune or inflammatory diseases. The previous genome-wide association study on type 1 AIH in a European population has reported a risk G allele of a single nucleotide polymorphism (SNP), rs4325730, in this region. Here, we conducted an association study of this SNP with type 1 AIH in a Japanese population, as a replication study.An association study of rs4325730 was conducted in 343 Japanese AIH patients and 315 controls.We found that rs4325730 is associated with AIH (P=0.0173, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.05-1.62, under the allele model for G allele, P=0.0070, OR 1.62, 95% CI 1.14-2.31, under the dominant model for G allele). This SNP was strongly associated with definite AIH (P=0.0134, OR 1.36, 95% CI 1.07-1.74; under allele model for G, P=0.0035, OR 1.85, 95% CI 1.22-2.81, under dominant model for G).This is the first replication association study of rs4325730 upstream of ICOS with AIH in the Japanese population and rs4325730G is a risk allele.
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Shomi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.affiliation: Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan.|NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Komori
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Abiru
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagaoka
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Naganuma
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Naeshiro
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shimada
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tomizawa
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Fujio
authors.initials: F
authors.lastname: Makita
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ario
authors.affiliation: Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan.|NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kawasaki
authors.affiliation: Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ohira
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan.|NHO-AIH study group, National Hospital Organization Nagasaki Medical Center, Omura, Japan.|Department of Gastroenterology and Rheumatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D019693:Hepatitis, Autoimmune / Q000235:genetics* / Q000473:pathology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein