title: Involvement of genes encoding apoptosis regulatory factors (FAS, FASL, TRAIL, BCL2, TNFR1 and TNFR2) in the pathogenesis of autoimmune thyroid diseases.
abstract: Apoptosis is necessary for the maintenance of self-tolerance by eliminating autoreactive immune cells in the periphery. To clarify the association between the pathogenesis of autoimmune thyroid disease (AITD) and genes encoding apoptosis regulatory factors, we genotyped the FAS -1377G/A, -670A/G, FASL -844C/T, TRAIL -716C/T, BCL2 -938C/A, +127G/A, TNFR1 -383A/C and TNFR2 +676T/G polymorphisms. The frequencies of the FASL -844CC and BCL2 -938AA genotypes were significantly lower in AITD patients than in control subjects (P=0.0101 and 0.0307, respectively). The frequency of the TNFR2 +676TT genotype was significantly lower in Graves' disease (GD) patients than in controls (P=0.0284). The serum sFasL level was significantly higher in GD and Hashimoto's disease (HD) patients than in control subjects (P=0.0003 and 0.0017, respectively). The serum sFasL levels in control subjects were significantly lower than those in intractable GD, GD in remission, and HD without treatment (P=0.0310, 0.0007 and 0.0002, respectively). The serum sFasL levels in HD with treatment were significantly lower than those in HD without treatment (P=0.0490). The polymorphisms in genes encoding apoptosis regulatory factors (FASL, BCL2) and serum levels of sFasL may be associated with immune dysregulation.
authors.affiliation: Department of Biomedical Informatics, Division of Health Sciences, Osaka University, Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan; Laboratory for Clinical Investigation, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Department of Biomedical Informatics, Division of Health Sciences, Osaka University, Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Biomedical Informatics, Division of Health Sciences, Osaka University, Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ishido
authors.affiliation: Department of Biomedical Informatics, Division of Health Sciences, Osaka University, Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Kodu
authors.affiliation: Department of Biomedical Informatics, Division of Health Sciences, Osaka University, Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Maruoka
authors.affiliation: Department of Biomedical Informatics, Division of Health Sciences, Osaka University, Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Katsumata
authors.affiliation: Laboratory for Clinical Investigation, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Hidaka
authors.affiliation: Department of Biomedical Informatics, Division of Health Sciences, Osaka University, Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: iwatani@sahs.med.osaka-u.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Iwatani
mesh_terms: D000328:Adult; D000483:Alleles; D017209:Apoptosis / Q000235:genetics; D018450:Disease Progression; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D013967:Thyroiditis, Autoimmune / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics
chemical_list: C000595707:BCL2 protein, human; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D019014:fas Receptor
keywords: Apoptosis; Autoimmune thyroid disease; Intractability; Polymorphism; Severity