Interleukin-1-beta gene, but not the interleukin-1 receptor antagonist gene, is associated with Graves' disease.
Interleukin-1 (IL-1) is considered to be involved in the pathogenesis of Graves' disease. The aim of this study was to test whether the IL-1-beta gene promoter region and exon 5 and IL-1 receptor antagonist (IL-1Ra) gene intron 2 polymorphisms could be useful genetic markers for susceptibility to Graves' disease. A normal control group of 163 healthy people and another group of 95 patients with Graves' disease were examined. Polymerase chain reaction (PCR) was used to analyze the variable number of tandem repeats (VNTRs) at intron 2 of the IL-1Ra gene for the polymorphism. PCR-based restriction analysis was done for the IL-1-beta gene polymorphisms of the promoter region and exon 5 using endonucleases AvaI and TaqI, respectively. We found significantly increased frequencies of the C/C homozygous genotype (chi(2) test, P=0.038; odds ratio (OR)=2.558, 95% confidence interval (CI)=1.205-5.430) and the C allele (chi(2) test, P=0.011; OR=1.589, 95% CI=1.094-2.309) in the IL-1-beta gene promoter (-511 C/T polymorphism) in Graves' disease patients compared to normal controls. There were no significant differences in polymorphisms of IL-1-beta gene exon 5 and IL-1Ra gene intron 2 between the patient and normal control groups. A subgroup analysis also demonstrated no association between the severity of the disease and any polymorphism of IL-1-related genes. We suggest that the IL-1-beta gene promoter polymorphism can be used as a genetic marker for susceptibility to Graves' disease. It is worthwhile to study the cytokine genes further because of the association between cytokines and Graves' disease.
Chen
Rong-Hsing
RH
Department of Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Chen
Wen-Chi
WC
Chang
Chwen-Tzuei
CT
Tsai
Chang-Hai
CH
Tsai
Fuu-Jen
FJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta