title: PCSK9 polymorphism in a Tunisian cohort: identification of a new allele, L8, and association of allele L10 with reduced coronary heart disease risk.
abstract: 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.
authors.affiliation: Research Unit: UR 12ES09 Dyslipidemia and Atherogenesis, Faculty of Medicine, Monastir 5000, Tunisia. Electronic address: afefslimani@yahoo.com.
authors.forename: Afef
authors.initials: A
authors.lastname: Slimani
authors.affiliation: Laboratory of Molecular Biology, University of Pharmacy, Monastir 5000, Tunisia.
authors.forename: Mohamed Yahia
authors.initials: MY
authors.lastname: Hrira
authors.affiliation: Research Unit: UR 12ES09 Dyslipidemia and Atherogenesis, Faculty of Medicine, Monastir 5000, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Najah
authors.affiliation: Department of Cardiovascular Diseases, Fattouma Bourguiba Hospital, Monastir 5000, Tunisia.
authors.forename: Walid
authors.initials: W
authors.lastname: Jomaa
authors.affiliation: Department of Cardiovascular Diseases, Fattouma Bourguiba Hospital, Monastir 5000, Tunisia.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Maatouk
authors.affiliation: Department of Cardiovascular Diseases, Fattouma Bourguiba Hospital, Monastir 5000, Tunisia.
authors.forename: Khaldoun Ben
authors.initials: KB
authors.lastname: Hamda
authors.affiliation: Faculté de Pharmacie, Université Saint Joseph, Bierut, Lebanon; LVTS, INSERM U1148, Laboratory for Vascular Translational Science & Université Denis Diderot, Paris, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Abifadel
authors.affiliation: 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.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rabès
authors.affiliation: LVTS, INSERM U1148, Laboratory for Vascular Translational Science & Université Denis Diderot, Paris, France; AP-HP, CHU Xavier Bichat, Département de Génétique, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.affiliation: UR 4-Vieillissement, Stress, Inflammation, Un iversité Pierre et Marie Curie, Paris, France.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Rouis
authors.affiliation: Research Unit: UR 12ES09 Dyslipidemia and Atherogenesis, Faculty of Medicine, Monastir 5000, Tunisia.
authors.forename: Mohamed Naceur
authors.initials: MN
authors.lastname: Slimane
authors.affiliation: LVTS, INSERM U1148, Laboratory for Vascular Translational Science & Université Denis Diderot, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Varret
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics*; D012044:Regression Analysis; D017384:Sequence Deletion; D012697:Serine Endopeptidases / Q000235:genetics*; D014416:Tunisia; D044465:White People / Q000235:genetics*
chemical_list: C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Coronary artery disease; PCSK9 gene; c.61_63dupCTG; rs72555377