title: Polymorphisms in the genes encoding TGF-beta1, TNF-alpha, and IL-6 show association with type 1 diabetes mellitus in the Slovak population.
abstract: Numerous cytokines have been shown to participate in the pathogenesis of type 1 diabetes (T1D). As gene polymorphisms can influence cytokine production or function, they may potentially contribute to genetic predisposition to the disease. The aim of this study was therefore to investigate the role of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine and cytokine receptor genes in genetic susceptibility to T1D. Polymerase chain reaction with sequence-specific primers was used to genotype cytokine SNPs and HLA-DRB1 alleles in 151 diabetics and 140 healthy individuals of Slovak origin. Univariate analysis showed that transforming growth factor (TGF)-beta1 codon 10 TT homozygotes were significantly more susceptible to developing T1D than C allele carriers (P (c) = 0.0066, OR = 2.46). Furthermore, tumor necrosis factor (TNF)-alpha -308 A allele carriers were also significantly overrepresented among the diabetics (P (c) = 0.0031, OR = 2.62); however, the association of the -308 A allele with T1D might be due to its strong linkage disequilibrium with the susceptibility allele HLA-DRB1*0301. An association was also found with interleukin (IL)-6 -174 G/C and nt565 G/A SNPs; however, its significance was lost when statistical correction was applied. These data suggest that the TGF-beta1 codon 10 SNP is among numerous genetic variations with small individual effects on T1D development. Moreover, a possible role of TNF-alpha and IL-6 SNPs cannot be ruled out, although their association with T1D was due to strong LD with the HLA class II susceptibility allele or did not withstand statistical correction, respectively.
authors.affiliation: Department of Immunology, Faculty of Medicine, Comenius University, Odborarske nam. 14, 813 72 Bratislava 1, Slovakia. jurajjavor@gmail.com
authors.forename: Juraj
authors.initials: J
authors.lastname: Javor
authors.forename: Stanislav
authors.initials: S
authors.lastname: Ferencik
authors.forename: Maria
authors.initials: M
authors.lastname: Bucova
authors.forename: Martina
authors.initials: M
authors.lastname: Stuchlikova
authors.forename: Emil
authors.initials: E
authors.lastname: Martinka
authors.forename: Lubomir
authors.initials: L
authors.lastname: Barak
authors.forename: Lujza
authors.initials: L
authors.lastname: Strbova
authors.forename: Hans
authors.initials: H
authors.lastname: Grosse-Wilde
authors.forename: Milan
authors.initials: M
authors.lastname: Buc
mesh_terms: D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D018154:Slovakia; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D018836:Inflammation Mediators; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha