title: Association analysis of the NOD2 gene with susceptibility to graft-versus-host disease in a Japanese population.
abstract: Members of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family participate in the innate immune system, exerting widespread effects on cytokine secretion, autophagy, and apoptosis. Recent studies in Caucasians revealed the association between mutants of NOD2, a member of the NLR family, and severity of acute graft-versus-host disease (GVHD). NOD2 polymorphism screening has been recommended for donor selection and risk assessment at bone marrow transplantation. To investigate whether NOD2 plays a role in the pathogenesis of GVHD in a Japanese population, we examined DNA from 142 bone marrow transplant patient/donor pairs to detect genetic variation in the NOD2 gene. No genetic variants of NOD2 were associated with the severity of acute GVHD in our patients. However, a weak association between a single nucleotide polymorphism in the NOD2 gene (R471C) and acute myeloid leukemia in the bone marrow patients (p = 0.029, odds ratio 4.08, 95% CI 1.22-13.67) was detected. This polymorphism was not prevalent in 479 Crohn's disease (CD) patients in Japan. These results suggest that, in the Japanese population, unlike the Caucasian, NOD2 is not a major contributor to susceptibility to severe acute GVHD.
authors.affiliation: Department of Public Health, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan. ttanabe@med.shimane-u.ac.jp.|Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan. ttanabe@med.shimane-u.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tanabe
authors.affiliation: Department of Public Health, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.|Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
authors.forename: Natsu
authors.initials: N
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Laboratory for Genotyping Development, Center for Genomic Medicine, The Institute of Physical and Chemical Research, Kanagawa, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Hematology and Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Hematology and Oncology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
authors.affiliation: Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Onizuka
authors.affiliation: Department of Human Pathology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
authors.affiliation: Hematology Division, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Hematology and Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ishikawa
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.affiliation: Division of Hematology, Ehime Prefectural Central Hospital, Ehime, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hara
authors.affiliation: Department of Pediatrics, Ibaraki Children's Hospital, Mito, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Koike
authors.affiliation: Department of Hematology/Oncology, Osaka Medical Center, Research Institute for Maternal and Child Health, Izumi, Japan.
authors.forename: Keisei
authors.initials: K
authors.lastname: Kawa
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Takakazu
authors.initials: T
authors.lastname: Kawase
authors.affiliation: Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Department of Public Health, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Amano
authors.affiliation: Department of Public Health, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Kobayashi-Miura
authors.affiliation: Department of Hygiene and Preventive Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Takeyasu
authors.initials: T
authors.lastname: Kakamu
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Chemistry/Biological Chemistry, Integrative Bioscience and Bioengineering, Advanced Sciences and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Asano
authors.affiliation: Department of Public Health, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
mesh_terms: D000483:Alleles; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D007564:Japan; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein