Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Apr 1:13:46.
doi: 10.1186/2251-6581-13-46. eCollection 2014.

TNF-α and IFN-γ gene variation and genetic susceptibility to type 1 diabetes and its microangiopathic complications

Javad Tavakkoly Bazzaz  1 , Mahsa M Amoli  2 , Zahra Taheri  2 , Bagher Larijani  2 , Vera Pravica  3 , Ian V Hutchinson  3
Affiliations

TNF-α and IFN-γ gene variation and genetic susceptibility to type 1 diabetes and its microangiopathic complications

Javad Tavakkoly Bazzaz et al. J Diabetes Metab Disord. .

Abstract

Background: TNF-α has accelerating role in development of type 1 diabetes. Although an immunosupressor function and leading protecting role in T1DM also has been claimed for this pro-inflammatory cytokine. Over-expression of pro-inflammatory and type 1 cytokines (Th1, like IFN-γ) drive insulitis toward the destructive form that leads to type 1 diabetes (T1DM). Among type 1 cytokines only IFN-γ has been detectable in the islet β cells. In deletion studies IFN-γ was also the only Th1 cytokine for which its ablation or blockade caused delayed or decreased incidence of T1DM.

Methods: Functional polymorphisms of TNF-α at position -308*G/A and at position +874*T/A of IFN-γ gene were employed as markers and the comparative distribution of derived genotypes/alleles were assessed in 248 British Caucasian T1DM patients and 118 healthy controls.

Results: There was no significant association between IFN-γ gene polymorphism and T1DM or the diabetic complication triad. There was a marginal association between TNF-α -308*G/A polymorphism in nephropaths (vs healthy controls) (p = 0.06), which its insignificancy may be due to survivor factor. No significant association was evident between the genotype/allele of the applied marker and T1DM or diabetic complication triad.

Conclusion: Our results are in contrast with previous reports suggesting that these polymorphisms are not related to T1DM. This study also underlines the importance of replication of association studies to confirm the previous interpretation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Microvascular diabetic complications according to the age at the onset of diabetes (under or over 15 years).
See this image and copyright information in PMC

References

    1. Hajeer AH, Hutchinson IV. Influence of TNFalpha gene polymorphisms on TNFalpha production and disease. Hum Immunol. 2001;62:1191–1199. doi: 10.1016/S0198-8859(01)00322-6. - DOI - PubMed
    1. Balkwill F. Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev. 2002;13:135–141. doi: 10.1016/S1359-6101(01)00020-X. - DOI - PubMed
    1. Vilcek J, Lee TH. Tumor necrosis factor. New insights into the molecular mechanisms of its multiple actions. J Biol Chem. 1991;266:7313–7316. - PubMed
    1. McSorley SJ, Soldera S, Malherbe L, Carnaud C, Locksley RM, Flavell RA, Glaichenhaus N. Immunological tolerance to a pancreatic antigen as a result of local expression of TNFalpha by islet beta cells. Immunity. 1997;7:401–409. doi: 10.1016/S1074-7613(00)80361-1. - DOI - PubMed
    1. Shalaby MR, Espevik T, Rice GC, Ammann AJ, Figari IS, Ranges GE, Palladino MA Jr. The involvement of human tumor necrosis factors-alpha and -beta in the mixed lymphocyte reaction. J Immunol. 1988;141:499–503. - PubMed

LinkOut - more resources