The genetic diversity of proteasome genes in the T1DM Polish population



Autoimmune metabolic diseases generate numerous healthy and social problems. The possible association of SNPs in the ubiquitin-proteasome system (UPS) with human pathology is under intensive study.



In the present study, the genetic variations in PSMB5 (rs11543947), PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) UPS gene cluster was investigated in type 1 diabetes and healthy donors in the Polish population.



The study comprised 105 patients with type 1 diabetes mellitus (T1DM) and 214 controls. All were genotyped by PCR and restriction digestion analysis or Sanger sequencing.



Rs1048990 and rs2348071 were found to be neutral to T1DM (p-value: 0.499 and 0.656, respectively). According to the multiple loci genotype (MLG) analysis, the major homozygote of the tested polymorphisms had a protective effect. The most common MLG in the T1DM group was characterised by simultaneous risk factors at rs11543947, rs2277460, rs2295826 and rs2295827 (p-value: <0.0001 vs. MGL1). Multiple locus haplotype analysis revealed a similar dependence, with common alleles at all tested loci demonstrating a protective effect, and the rare alleles increasing T1DM risk (p-value: <0.0001 vs. MLH1).



Our study suggests that the proteasome gene polymorphisms rs11543947, rs2277460, rs2295826, and rs2295827 could be potential markers for T1DM susceptibility in the Polish population.
