ژنتيك ديابت نوع يك : بررسي نقش ژن TNF-A

GENETICS OF TYPE 1 DIABETES: STUDY OF TNF-alpha GENE

Background: Type 1 diabetes (T1DM) is an organ specific auto-immune disease, which is resulted by selective destruction of 13 islet cells. insulitis as the initial event prior to T1DM development is featured mainly by lymphocytic infiltration, that may recede frequently leading to healthy state (benign insulitis). Among the issues that govern which of these outcome lie ahead in insulitis are the genetic background of the host and also the immunological circumstances in 13 isletsʹ micro-environment. Methods: As a "case-control association study" the impact of a polymorphism within TNF-a gene at position -308*G/A on genetic susceptibility to TIDM is analyzed in a British-Caucasian population (248 cases and 118 healthy controls). Results: The distribution of genotype/allele frequencies between patients and controls did not reflect significant differences (p= NS). Conclusion: Since the crucial role of TNF-a in development of T1DM is well established, our data may confer that the examined polymorphic marker does not have functional effects on TNF-alpha. gene expression, influencing the local or systemic level of this pro-inflammatory cytokine. However, in addition to addressing the uncertainties in "genotype-phenoype" correlations in complex diseases (i.e. TIDM), the negative results of our study also may instead draw attention to the potential impacts of post-transcriptional regulatory mechanisms relative to gene structural-based regulatory systems.