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Cardiovasc Diabetol. 2011 Apr 17;10:32. doi: 10.1186/1475-2840-10-32.

Proteasome modulator 9 and macrovascular pathology of T2D.

Author information

  • Laboratory of Molecular Genetics of Complex and Monogenic Disorders, Department of Medicine and Cellular & Molecular Physiology and Biostatistics, Penn State University, M. S. Hershey Medical Center, Hershey, PA, USA. claudia.gragnoli@gmail.com

Abstract

AIMS:

Coronary artery disease (CAD) and stroke share a major linkage at the chromosome 12q24 locus. The same chromosome region entails at least a major risk gene for type 2 diabetes (T2D) within NIDDM2, the non-insulin-dependent-diabetes 2 locus. The gene of proteasome modulator 9 (PSMD9) lies in the NIDDM2 region and is implicated in diabetes in mice. PSMD9 mutations rarely cause T2D and common variants are linked to both late-onset T2D and maturity-onset-diabetes of the young (MODY3). In this study, we aimed at determining whether PSMD9 is linked to macrovascular pathology of T2D.

METHODS AND RESULTS:

In our 200 T2D families from Italy, we characterized the clinical phenotype of macrovascular pathology by defining the subjects for presence or absence of CAD, stroke and/or transitory ischemic attacks (TIA), plaques of the large arterial vessels (macro-vasculopathy) and arterial angioplasty performance. We then screened 200 T2D siblings/families for PSMD9 +nt460A/G, +nt437C/T and exon E197G A/G single nucleotide polymorphisms (SNPs) and performed a non-parametric linkage study to test for linkage for coronary artery disease, stroke/TIA, macro-vasculopathy and macrovascular pathology of T2D. We performed 1,000 replicates to test the power of our significant results. Our results show a consistent significant LOD score in linkage with all the above-mentioned phenotypes. Our 1000 simulation analyses, performed for each single test, confirm that the results are not due to random chance.

CONCLUSIONS:

In summary, the PSMD9 IVS3+nt460A/G, +nt437C/T and exon E197G A/G SNPs are linked to CAD, stroke/TIA and macrovascular pathology of T2D in Italians.

PMID:
21496327
[PubMed - indexed for MEDLINE]
PMCID:
PMC3102609
Free PMC Article
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