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Preliminary evaluation of proprotein convertase subtilisin/kexin type 5 mutations in lower extremity artery disease

Setalia Popa, Viviana Aursulesei, Eusebiu Vlad Gorduza, Irina Iuliana Costache

The low level of high-density lipoprotein cholesterol (HDL-c) is a major risk factor for atherosclerotic cardiovascular disease including Lower extremity artery disease (LEAD). The variability of proprotein convertase subtilisin/kexin type 5 (PCSK5) gene was proposed as regulator of HDL-c metabolism. The molecular mechanisms are not fully elucidated. Several studies suggest that several genetic anomalies could influence the risk of developing LEAD. Considering these data, the aim of our study was to identify PCSK5 gene variants in patients with LEAD using multiplex ligation-dependent probe amplification (MLPA) as a screening method. The study included 48 patients with LEAD documented by angiography. All patients had low levels of HDL-c and a high total cholesterol/HDL-c ratio. DNA extraction was performed using the precipitation method, while polymorphisms of all PCSK5 gene exons were assessed using MLPA. The MPLA results were subsequently analysed with Coffalyser® software. Analysis of PCSK5 gene expression showed normal genotype in 45 patients. Heterozygous deletion of exon 9 of PCSK5 gene was identified in only 3 patients and was not correlated with HDL-c values. Our data cannot establish a clear correlation between mutational profile of PCSK5 gene and LEAD, so more extensive genetic testing in larger cohorts are required.