Polymorphisms in the Genes Encoding TGF-β1, TNF-α, and IL-6 Show Association with Type 1 Diabetes Mellitus in the Slovak Population

  • Juraj Javor
  • Stanislav Ferencik
  • Maria Bucova
  • Martina Stuchlikova
  • Emil Martinka
  • Lubomir Barak
  • Lujza Strbova
  • Hans Grosse-Wilde
  • Milan Buc


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)-β1 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)-α −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-β1 codon 10 SNP is among numerous genetic variations with small individual effects on T1D development. Moreover, a possible role of TNF-α 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.


Cytokines Interleukin-6 Single nucleotide polymorphisms Transforming growth factor-β1 Tumor necrosis factor-α Type 1 diabetes 



This study was supported by the Research Program of the Ministry of Education of the Slovak Republic KEGA 3/7140/07, Comenius University Grant UK/25/2006, and a Short-Term Fellowship of European Federation of Immunological Societies.


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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2010

Authors and Affiliations

  • Juraj Javor
    • 1
  • Stanislav Ferencik
    • 2
  • Maria Bucova
    • 1
  • Martina Stuchlikova
    • 1
  • Emil Martinka
    • 4
  • Lubomir Barak
    • 5
  • Lujza Strbova
    • 6
  • Hans Grosse-Wilde
    • 3
  • Milan Buc
    • 1
  1. 1.Department of Immunology, Faculty of MedicineComenius UniversityBratislava 1Slovakia
  2. 2.Institute for Transfusion MedicineUniversity Hospital of EssenEssenGermany
  3. 3.Institute of ImmunologyUniversity Hospital of EssenEssenGermany
  4. 4.Department of DiabetologyNational Institute of Endocrinology and DiabetologyLubochnaSlovakia
  5. 5.1st Department of Pediatrics, Faculty of MedicineComenius UniversityBratislavaSlovakia
  6. 6.2nd Department of Internal Medicine, Faculty of MedicineComenius UniversityBratislavaSlovakia

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