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Open Access Open Badges Original investigation

Hypercholesterolemia and a candidate gene within the 12q24 locus

Claudia Gragnoli

Author Affiliations

Laboratory 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

Center for Biotechnology and Department of Biology, Temple University's College of Science & Technology, Philadelphia, PA, USA

Molecular Biology Laboratory, Bios Biotech Multi-Diagnostic Health Center, Rome, Italy

Cardiovascular Diabetology 2011, 10:38  doi:10.1186/1475-2840-10-38

Published: 9 May 2011



The 12q24 locus entails at least one gene responsible for hypercholesterolemia. Within the 12q24 locus lies the gene of proteasome modulator 9 (PSMD9). PSMD9 is in linkage with type 2 diabetes (T2D), T2D-nephropathy and macrovascular pathology in Italian families and PSMD9 rare mutations contribute to T2D.


In the present study, we aimed at determining whether the PSMD9 T2D risk single nucleotide polymorphisms (SNPs) IVS3 + nt460 A > G, IVS3 + nt437 T > C and E197G A > G are linked to hypercholesterolemia in 200 T2D Italian families.


We characterized 200 Italian families for presence and/or absence of hypercholesterolemia characterized by LDL levels ≥ 100 mg/dl in drug-naïve patients and/or presence of a diagnosis of hypercholesterolemia in a patient treated with statin medication. The phenotypes were described as unknown in all cases in which the diagnosis was either unclear or the data were missing. We tested in the 200 Italians families for evidence of linkage of the PSMD9 SNPs with hypercholesterolemia. The non-parametric linkage analysis was performed for the qualitative phenotype by using the Merlin software; the Lod score and correspondent P-value were calculated. For the significant linkage score, 1000 replicates were performed to calculate the empirical P-value.


The PSMD9 gene SNPs studied show linkage to hypercholesterolemia. The results are not due to random chance.


PSMD9 should be tested in all populations reporting linkage to hypercholesterolemia within the chromosome 12q24 locus. The impact of this gene on hypercholesterolemia and contribution to cardio- and cerebrovascular events may be high.

SNPs; PSMD9; Linkage; Hypercholesterolemia