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Hypercholesterolemia and a candidate gene within the 12q24 locus
1Laboratory of Molecular Genetics of Complex and Monogenic Disorders, Department of Medicine and Cellular & Molecular Physiology and Biostatistics, Penn State University and M.S. Hershey Medical Center, Hershey, PA, USA. claudia.gragnoli@gmail.com
Cardiovascular Diabetology
|May 11, 2011
Summary
The proteasome modulator 9 (PSMD9) gene SNPs are linked to hypercholesterolemia in Italian families. This finding suggests PSMD9 may play a role in cardiovascular health and warrants further investigation.
Area of Science:
- Genetics
- Cardiovascular Disease Research
- Metabolic Disorders
Background:
- The 12q24 chromosomal locus contains genes associated with hypercholesterolemia.
- Proteasome modulator 9 (PSMD9) gene is located within the 12q24 locus.
- PSMD9 is linked to type 2 diabetes (T2D), T2D-nephropathy, and macrovascular pathology.
Purpose of the Study:
- To investigate the association between PSMD9 single nucleotide polymorphisms (SNPs) and hypercholesterolemia.
- To determine if specific PSMD9 SNPs (IVS3 + nt460 A > G, IVS3 + nt437 T > C, E197G A > G) are linked to hypercholesterolemia in Italian families with T2D.
Main Methods:
- Characterization of 200 Italian families for hypercholesterolemia phenotypes.
- Utilizing non-parametric linkage analysis with Merlin software to assess linkage between PSMD9 SNPs and hypercholesterolemia.
- Calculating LOD scores and P-values, with empirical P-values determined through 1000 replicates for significant linkage.
Main Results:
- The studied PSMD9 gene SNPs demonstrated a significant linkage with hypercholesterolemia.
- The observed linkage is statistically significant and not attributable to random chance.
Conclusions:
- PSMD9 is a potential candidate gene for hypercholesterolemia, particularly within the 12q24 locus.
- Testing PSMD9 in populations with linkage to hypercholesterolemia is recommended.
- PSMD9 may significantly impact hypercholesterolemia and contribute to cardio- and cerebrovascular events.
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