title: Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers: a cross-sectional study in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.
abstract: Cytokines, including interleukin-6 (IL-6), play an important role in the liver. The aim of this study was to investigate associations between common polymorphisms in potential functional promoters of cytokine genes and liver damage markers among enrollees of a large Japanese cohort study. Subjects included 3257 Japanese individuals (1608 men and 1649 women, aged 35-69 years). Six single nucleotide polymorphisms (SNPs) in the promoter regions of five cytokine genes, IL1B (T-31C), IL6 (C-634G), IL8 (T-251A), IL10 (T-819C), tumor necrosis factor-A (TNFA) (T-1031C), and TNFA (C-857T), were genotyped by polymerase chain reaction. Information regarding alcohol intake, smoking habits, height, and weight was collected by a self-administered questionnaire. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured during a routine health check-up. Of the six SNPs genotyped, an IL6 polymorphism (rs1800796, C-634G) was most strongly associated with a liver damage marker, AST. Mean serum AST was significantly different among the three genotypes (mean ± SD, 22.7 ± 7.3 IU/L for CC, 22.8 ± 7.7 IU/L for CG, and 24.3 ± 8.6 IU/L for GG, p=0.011 by analysis of variance). The differences remained significant after adjustment for potential confounders by general linear models. The variations in mean serum AST and ALT levels were marked especially among men. Thus, the functional polymorphism IL6 C-634G may affect serum AST and ALT levels, possibly through different IL-6 production.
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: wakai@med.nagoya-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Suma
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tae
authors.initials: T
authors.lastname: Sasakabe
authors.affiliation: Chikushi Office for Health, Human Services and Environmental Issues, Fukuoka Prefectural Government, Onojo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Health Science, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takashima
authors.affiliation: Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.affiliation: Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Nagato
authors.initials: N
authors.lastname: Kuriyama
authors.affiliation: Department of Preventive Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kokichi
authors.initials: K
authors.lastname: Arisawa
authors.affiliation: Division of Cancer Registry, Prevention and Epidemiology, Chiba Cancer Center, Chiba, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.affiliation: Core for Genomic Medicine, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.affiliation: Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007564:Japan; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Alanine aminotransferase; Aspartate aminotransferase; Cross-sectional studies; Cytokine; Interleukin; Polymorphism