Joan Duran1, Pilar Sánchez-Olavarría2, Marina Mola3, Víctor Götzens1, Julio Carballo4, Eva Martín-Pelegrina4, Màrius Petit4, Bruno García Del Blanco5, David García-Dorado5, Josep M de Anta6. 1. Unidad de Anatomía y Embriología Humanas, Departamento de Patología y Terapéutica Experimental, Facultad de Medicina, Campus de Ciencias de la Salud de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain. 2. Unidad de Anatomía y Embriología Humanas, Departamento de Patología y Terapéutica Experimental, Facultad de Medicina, Campus de Ciencias de la Salud de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain; Departamento de Estadística, Universidad de Valparaíso, Valparaíso, Chile. 3. Unidad de Anatomía y Embriología Humanas, Departamento de Patología y Terapéutica Experimental, Facultad de Medicina, Campus de Ciencias de la Salud de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain; Grupo de Investigación Neurovascular (NEUVAS), IMIM-Hospital del Mar, PRBB-Parque de Investigación Biomédica de Barcelona, Barcelona, Spain. 4. Departamento de Cardiología y Hemodinamia, Centro Cardiovascular Sant Jordi, Barcelona, Spain. 5. Departamento de Cardiología, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 6. Unidad de Anatomía y Embriología Humanas, Departamento de Patología y Terapéutica Experimental, Facultad de Medicina, Campus de Ciencias de la Salud de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: janta@ub.edu.
Abstract
INTRODUCTION AND OBJECTIVES: Urokinase-type plasminogen activator, which is encoded by the PLAU gene, plays a prominent role during collateral arterial growth. We investigated whether the PLAU P141L (C > T) polymorphism, which causes a mutation in the kringle domain of the protein, is associated with coronary collateral circulation in a cohort of 676 patients with coronary artery disease. METHODS: The polymorphism was genotyped in blood samples using a TaqMan-based genotyping assay, and collateral circulation was assessed by the Rentrop method. Multivariate logistic regression models adjusted by clinically relevant variables to estimate odds ratios were used to examine associations of PLAU P141L allelic variants and genotypes with collateral circulation. RESULTS: Patients with poor collateral circulation (Rentrop 0-1; n = 547) showed a higher frequency of the TT genotype than those with good collateral circulation (Rentrop 2-3; n = 129; P = .020). The T allele variant was also more common in patients with poor collateral circulation (P = .006). The odds ratio of having poorly developed collaterals in patients bearing the T allele (adjusted for clinically relevant variables) was statistically significant under the dominant model (odds ratio = 1.83 [95% confidence interval, 1.16-2.90]; P = .010) and the additive model (odds ratio = 1.73 [95% confidence interval, 1.14-2.62]; P = .009). CONCLUSIONS: An association was found between coronary collateral circulation and the PLAU P141L polymorphism. Patients with the 141L variant are at greater risk of developing poor coronary collateral circulation.
INTRODUCTION AND OBJECTIVES:Urokinase-type plasminogen activator, which is encoded by the PLAU gene, plays a prominent role during collateral arterial growth. We investigated whether the PLAUP141L (C > T) polymorphism, which causes a mutation in the kringle domain of the protein, is associated with coronary collateral circulation in a cohort of 676 patients with coronary artery disease. METHODS: The polymorphism was genotyped in blood samples using a TaqMan-based genotyping assay, and collateral circulation was assessed by the Rentrop method. Multivariate logistic regression models adjusted by clinically relevant variables to estimate odds ratios were used to examine associations of PLAUP141L allelic variants and genotypes with collateral circulation. RESULTS:Patients with poor collateral circulation (Rentrop 0-1; n = 547) showed a higher frequency of the TT genotype than those with good collateral circulation (Rentrop 2-3; n = 129; P = .020). The T allele variant was also more common in patients with poor collateral circulation (P = .006). The odds ratio of having poorly developed collaterals in patients bearing the T allele (adjusted for clinically relevant variables) was statistically significant under the dominant model (odds ratio = 1.83 [95% confidence interval, 1.16-2.90]; P = .010) and the additive model (odds ratio = 1.73 [95% confidence interval, 1.14-2.62]; P = .009). CONCLUSIONS: An association was found between coronary collateral circulation and the PLAUP141L polymorphism. Patients with the 141L variant are at greater risk of developing poor coronary collateral circulation.
Authors: Joan Duran; Pilar Sánchez Olavarría; Marina Mola; Víctor Götzens; Julio Carballo; Eva Martín Pelegrina; Màrius Petit; Omar Abdul-Jawad; Imanol Otaegui; Bruno García del Blanco; David García-Dorado; Josep Reig; Alex Cordero; Josep Maria de Anta Journal: BMC Cardiovasc Disord Date: 2015-05-12 Impact factor: 2.298