Wilhelm bernhard workshop on the cell nucleus


THE NUCLEAR MATRIX PROTEIN PSMA6 GENE INTRONIC MICROSATELLITE ALLELE IS ASSOCIATED WITH TYPE II DIABETES MELLITUS



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THE NUCLEAR MATRIX PROTEIN PSMA6 GENE INTRONIC MICROSATELLITE ALLELE IS ASSOCIATED WITH TYPE II DIABETES MELLITUS

Sjakste N1, Kalis M1, Pirags V1, Lazdins M1, Groop L2

1University of Latvia, Riga, Latvia and 2Department of Endocrinology, Lund University, University Hospital Malmö, Sweden
Proteasomes are ubiquitous particles with multicatalytic proteinase activity aimed on degradation of ubiquinated proteins including transcription factors, oncogene products, etc. Alterations of the proteasome functions and structure lead to numerous pathologies. Proteasomes compose an integral part of the nuclear matrix, where PSMA 6 protein is found among other proteasomal proteins. This study was aimed on a search for correlation of the TG dinucleotide repeat polymorpfism (HSMS006) in the 6th intron of the human proteasome core particle PSMA6 gene and Type II diabetes mellitus. Polymorphism studies of the microsatellite tract length were performed in non-insulin dependent diabetes mellitus patients (91 individuals from Botnia (Sweden) and 66 from Latvia) compared to a control group (88 age-matched individuals with normal insulin sensitivity from Botnia and 33 from Latvia) using PCR and DNA fragment length determination. In the control groups we have revealed 10 alleles presented by 13 to 25 TG repeats, alleles with 18 and 21 repeats being the most frequent. Allele distribution in Botnic and Latvian populations were similar. In Type 2 diabetes patients from both populations the (TG)22 allele was two times more frequent as compared to the corresponding control group. It appears that polymorphism of the TG repeat in the 6th intron of the human proteasome core particle PSMA6gene is correlated to Type II diabetes mellitus morbidity.


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