Proinflammatory cytokine gene polymorphisms among Hashimoto's thyroiditis patients.
Proinflammatory cytokines are involved in the pathogenesis of Hashimoto's thyroiditis (HT). To test whether certain specific proinflammatory cytokine gene polymorphisms could be genetic markers for an individual's susceptibility to HT, we investigated single-site polymorphisms of certain proinflammatory cytokine genes of interest for 107 HT sufferers and 163 controls, subsequent to preparing the necessary experimental genomic DNA from peripheral blood, using a polymerase chain reaction (PCR)-based restriction analysis. The polymorphisms we detected were as follows: 1) C/T and E1/E2 polymorphisms for the interleukin (IL)-1beta gene at promoter (-511) and exon 5, respectively; 2) a variable number of tandem repeats (VNTRs) for the IL-1 receptor antagonist (IL-1Ra) gene at intron 2; 3) a C/G polymorphism for the IL-6 gene at promoter (-572); and 4) an A/G polymorphism for the tumor necrosis factor (TNF)-alpha gene at promoter (-308). The data demonstrated an increased ratio of CG genotype and decreased ratios of CC and GG genotypes (chi-squared test; P = 0.025) for the IL-6 gene promoter for HT patients when compared with normal controls. The odds ratio (OR) for the CG genotype, as compared to the GG genotype, for HT patients was shown to be 4.065 (95% confidence interval (CI): 1.268-13.032). Comparison of the genotype analysis for the remaining gene polymorphisms and the allelic analysis for all of the screened gene polymorphisms, however, all revealed no statistically significant difference between the two study groups as regards frequency of genotype. In conclusion, we suggest that an IL-6 gene promoter (-572) C/G polymorphism could represent a potential "candidate" genetic marker to predict an individual's susceptibility to HT.
Chen
Rong-Hsing
RH
Department of Medicine, China Medical University Hospital, China Medical University, China.
Chang
Chwen-Tzuei
CT
Chen
Wei-Chi
WC
Tsai
Chang-Hai
CH
Tsai
Fuu-Jen
FJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D050031:Hashimoto Disease / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D017931:DNA Primers; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha