Aims
Controversial
Conclusion
PSMA6 rs_1048990 polymorphism may contribute to MI susceptibility in type 2 diabetes. Up-regulation of ubiquitin-proteasome pathway may be a potential mechanism for explaining such association.
Methods
224 subjects (73 patients with MI and 151 controls) were genotypized for variants of PSMA6 gene. In 36 patients, biopsy specimens were taken from the left ventricle area of presumed ischemia for ubiquitin-proteasome activity quantification.
Results
Allele frequency and genotype distribution of all PSMA6 gene polymorphisms studied did not differ between patients with MI and controls. When the analysis was restricted to type 2 diabetics (n=119), a different rs_1048990 C/G allele frequency and genotype distribution was found having diabetic subjects with MI (n=34) higher G allele frequency compared to controls (n=85), (p=0.02). Myocardial ubiquitin levels (r=0.75; p<0.001) and proteasome 20S (r=0.7; p<0.01) activity significantly correlated with plasma glucose even after adjusting for covariates. Type 2 diabetic subjects had higher myocardial ubiquitin levels (p<0.001) and proteasome 20S activity (p<0.001) compared to non-diabetics. Subjects carriers the allele G at rs_1048990 loci had higher myocardial ubiquitin levels and proteasome 20S activity.