HLA, CTLA-4 and TNF-beta Gene Polymorphisms and Disease Susceptibility in Korean Children with Graves' Disease / 대한내분비학회지

BACKGROUND: Graves' disease(GD) is an organ-specific autoimmune disorder that is inherited as a complex trait. At present three loci, namely the human leukocyte antigen(HLA), the cytotoxic T lymphocyte antigen-4(CTLA-4) and a thyroid stimulating hormone receptor(TSHR) are the only well-known genetic determinants for GD. To understand the mechanisms underlying the development of GD, we investigated the relationship of HLA alleles, polymorphisms of CTLA-4 gene and the tumor necrosis factor(TNF)-beta gene, with the disease susceptibility. METHODS: Fifty-two Korean children with GD(45 girls and 7 boys), and 119 healthy children, were investigated in this study. The HLA alleles were determined by a standard lymphocyte microtoxicity technique, ARMS-PCR(Amplification Refractory Mutation System-Polymerase Chain Reaction), PCR-SSP(Sequence Specific Primer) and PCR-SSOP(Sequence Specific Oliogonucleotide Probe) method. The CTLA-4 gene polymorphism was analyzed by PCR-SSCP(Single Strand Conformation Polymorphism), and the TNF-beta gene polymorphism by PCR-RFLP(Restriction Fragment Length Polymorphism). RESULTS: (1) The frequencies of HLA-A2, B46, DRB1*08 and DPB1*0202 were significantly increased, and those of HLA-A24, DQA1*01 and DQB1*05 were significantly decreased, in the GD patients compared to the control subjects. (2) A significant difference in the distributions of the AA, AG, and GG genotypes of the CTLA-4 exon 1 were observed between the GD patients and the control subjects, and a significant increase in the frequency of the G (alanine) allele was seen in the GD patients compared with the control subjects(84.6% vs 63.4%; RR=3.2; p or =45% compared with GD patients having TSHRAb <45%(37.5% vs 3.6%; RR=14.8; p<0.01). CONCLUSION: These data suggest that HLA-A2, B46, Cw*0102, DRB1*08 and DPB1*0202 are markers for disease susceptibility, and that HLA-A24, DQA1*01 and DQB1*05 are markers for disease protection, in Korean children with GD. This study showed that the CTLA-4 gene polymorphism was an additional marker of susceptibility in the GD patients, and was associated with exophthalmos, and that the TNF-beta gene polymorphism was associated with the TSHRAb activity.

Expression of Genetic Polymorphism of Interleukin-10 (IL-10) and Tumor Necrosis Factor-beta (TNF-beta) in Patients with Atopic Dermatitis / 대한피부과학회지

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease. Atopic dermatitis is associated with increased IL-4, IL-5, IL-10 and IL-13 but decreased INF-gamma and TNF production. IL-10 production has been implicated in autoimmunity because of its effect on B-cell proliferation and antibody production. The study of IL-10 gene polymorphism is of interest because of the pivotal role of IL-10 in the regulation of inflammatory and immune responses. TNF-beta significantly upregulates INF-gamma but downregulates IL-5, IL-13 and IgE, which suggests a potential role of TNF-beta in the pathogenesis of atopic dermatitis. OBJECTIVES: We have investigated polymorphism of IL-10 promoter gene and TNF-beta gene. METHODS: Seventy one patients with atopic dermatitis and one hundred and sixty six normal subjects participated in this study with analysis of polymorphism of IL-10 promoter (-1082), (-819) gene and seventy one patients with atopic dermatitis and one hundred and forty one normal subjects participated in the analysis of polymorphism of TNF-beta gene. The patients in this study were recently diagnosed with atopic dermatitis. RESULTS: The frequency of IL-10 promoter (-1082) genotypes (A/A, A/G, G/G), genes (A, G), IL-10 promoter (-819) genotypes (T/T, T/C, C/C) and genes (T, C) did not show any significant difference between atopic dermatitis patients and normal controls. There was no significant difference in the frequency of TNFB genotypes (TNFB*1/TNFB*1, TNFB*1/TNFB*2, TNFB*2/TNFB*2) and genes (TNFB*1, TNFB*2) in patients of atopic dermatitis and normal controls. CONCLUSION: The results of this study suggest that the other regions of the IL-10 promoter gene and TNFB gene should be investigated for polymorphism of atopic dermatitis. And the difference of IL-10 promoter and TNFB gene polymorphism between caucasian and Korean needs to be evaluated.