PCSK9 polymorphism in a Tunisian cohort: identification of a new allele, L8, and association of allele L10 with reduced coronary heart disease risk.

Autor: Slimani A; Research Unit: UR 12ES09 Dyslipidemia and Atherogenesis, Faculty of Medicine, Monastir 5000, Tunisia. Electronic address: afefslimani@yahoo.com., Hrira MY; Laboratory of Molecular Biology, University of Pharmacy, Monastir 5000, Tunisia., Najah M; Research Unit: UR 12ES09 Dyslipidemia and Atherogenesis, Faculty of Medicine, Monastir 5000, Tunisia., Jomaa W; Department of Cardiovascular Diseases, Fattouma Bourguiba Hospital, Monastir 5000, Tunisia., Maatouk F; Department of Cardiovascular Diseases, Fattouma Bourguiba Hospital, Monastir 5000, Tunisia., Hamda KB; Department of Cardiovascular Diseases, Fattouma Bourguiba Hospital, Monastir 5000, Tunisia., Abifadel M; Faculté de Pharmacie, Université Saint Joseph, Bierut, Lebanon; LVTS, INSERM U1148, Laboratory for Vascular Translational Science & Université Denis Diderot, Paris, France., Rabès JP; LVTS, INSERM U1148, Laboratory for Vascular Translational Science & Université Denis Diderot, Paris, France; AP-HP, Hôpital A. Paré, Boulogne-Billancourt & UFR des Sciences de la Santé, Université Versailles Saint Quentin-en-Yvelines, France., Boileau C; LVTS, INSERM U1148, Laboratory for Vascular Translational Science & Université Denis Diderot, Paris, France; AP-HP, CHU Xavier Bichat, Département de Génétique, Paris, France., Rouis M; UR 4-Vieillissement, Stress, Inflammation, Un iversité Pierre et Marie Curie, Paris, France., Slimane MN; Research Unit: UR 12ES09 Dyslipidemia and Atherogenesis, Faculty of Medicine, Monastir 5000, Tunisia., Varret M; LVTS, INSERM U1148, Laboratory for Vascular Translational Science & Université Denis Diderot, Paris, France.
Jazyk: angličtina
Zdroj: Molecular and cellular probes [Mol Cell Probes] 2015 Feb; Vol. 29 (1), pp. 1-6. Date of Electronic Publication: 2014 Sep 18.
DOI: 10.1016/j.mcp.2014.09.001
Abstrakt: The c.61_63dupCTG (L10) allele of rs72555377 polymorphism in PCSK9 has been reported to be associated with low-density lipoprotein-cholesterol (LDL-C) levels and with a decreased risk of coronary artery disease (CAD). We investigated the effect of two known alleles for rs72555377, L10 and L11, on the risk of CAD in a Tunisian cohort (218 patients diagnosed by angiography and 125 control subjects). Two subgroups of patients were defined by their level of stenosis: ≥50% for CAD and <50% for no-CAD. The genotypes were obtained by the size measurement of fluorescent-labeled PCR products. We identified a novel allele for the rs72555377 polymorphism: an in-frame deletion, c.61_63delCTG (L8). The frequency of the L10 allele was significantly higher in the no-CAD subgroup than in the CAD subgroup (0.210 vs 0.114, p = 0.045), and than in the subgroup of CAD patients presenting a stenosis ≥50% in two or three major coronary arteries (0.210 vs 0.125, p = 0.028). Multiple regression analysis showed that the L10 allele was significantly associated with a reduced risk of CAD (p = 0.049, OR = 0.51[0.26-1.00]), and with its reduced severity (p = 0.045, OR = 0.44[0.20-0.98]). The L10 allele is associated with a reduced risk and severity of CAD, seemingly independently of its LDL-lowering effect, suggesting a direct effect of PCSK9 on atherogenesis.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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