Endocrine Abstracts

Introduction: A possible involvement of proteasomes in the pathogenesis of type II diabetes mellitus has been recently reported. Therefore, association of polymorphism of proteosomal genes with type II diabetes mellitus is of particular interest. In this study, molecular markers of the proteasomal alpha subunit 6 gene PSMA6 and its adjacent genomic sites have been analyzed.

The goal of this study was to characterize polymorphisms of the HSMS801, HSMS702, HSMS701 and HSMS602 HSMS006 HSMS602 microsatellite repeats and SNPs at positions –110 and –8 from the translation start of PSMA6 gene and to investigate their eventual association with type II diabetes mellitus.

Methods: In this study, 250 DNA samples of type II diabetes and healthy controls were used. Genotyping was performed using allele-specific PCR and restriction fragment analysis.

Results: For the HSMS006 marker, the 193 bp allele was more common the group of cases rather than controls (0.154 and 0.085 respectively, P=4.64%). HSMS801 allele of 155 bp was found more often in the control group, as the HSMS602 marker allele of 169 bp. HSMS801 genotype of 148 bp/152 bp was more frequent in the control group (0.000 and 0.041 respectively, P=4.22%). Significant differences were observed between cases and controls in all ten haplotype distributions created by combinations of all the microsatellites by two. In these combinations linkage disequilibrium was revealed, indicating the non-random association of alleles in two or more loci on a chromosome. Genotype –8CG was significantly more frequent in type 2 diabetes patients, and haplotype C⁻¹¹⁰/G⁻⁸, compared to C⁻¹¹⁰/C⁻8 was associated with a higher risk of type II diabetes.

Conclusion: These results show association between microsatellite and SNP alleles of PSMA6 gene and its adjacent genomic sites with type II diabetes mellitus.