MANGANESE SUPEROXIDE-DISMUTASE (SOD2) GENE POLYMORPHISM IN INSULIN-DEPENDENT DIABETES-MELLITUS

Interleukin 1 (IL-1) is selectively cytotoxic to the insulin producing beta cell of pancreatic islets. This effect may be due to IL-1 induce d generation of reactive oxygen species and nitric oxide. Since beta c ells contain low amounts of the superoxide radical scavenger enzyme ma nganese superoxide dismutase (MnSOD), this may leave beta cells more s usceptible to IL-1 than other cell types. Genetic variation in the MnS OD locus could reflect differences in scavenger potential. We, therefo re, studied possible restriction fragment length polymorphisms (RFLPs) of this locus in patients with insulin-dependent diabetes mellitus (I DDM) (n=154) and control individuals (n=178). TaqI revealed a double d iallelic RFLP in patients as well as in controls. No overall differenc e in allelic or genotype frequencies were observed between IDDM patien ts and control individuals (p=0.11) and no significant association of any particular RFLP pattern with IDDM was found. Structurally polymorp hic MnSOD protein variants with altered activities have been reported. If genetic variation results in MnSOD variants with I educed activiti es, the MnSOD locus may still be a candidate gene for IDDM susceptibil ity. Whether the RFLPs reported in this study reflects differences in gene expression level, protein level and/or specific activity of the p rotein is yet to be studied.