title: Receptor-interacting protein 2 (RIP2) gene polymorphisms are associated with increased risk of subclinical atherosclerosis and clinical and metabolic parameters. The Genetics of Atherosclerotic Disease (GEA) Mexican study.
abstract: The receptor-interacting protein 2 (Rip2) is a serine/threonine kinase involved in multiple nuclear factor-κB (NFκB) activation pathways and is a key regulator of cellular lipid metabolism and cardiovascular disease. The aim of the present study was to evaluate the role of RIP2 gene polymorphisms as susceptibility markers for subclinical atherosclerosis (SA). Using an informatics analysis, four RIP2 gene polymorphisms with predicted functional effects (rs2293808, rs43133, rs431264, and rs16900627) were selected. The polymorphisms were genotyped in 405 individuals with SA (calcium score>0 assessed by computed tomography) and 1099 controls (calcium score=0). Clinical, anthropometric, tomographic and biochemical traits were measured. The association between the RIP2 polymorphisms and SA was evaluated using logistic regression analyses. Pair wise linkage disequilibrium (LD, D') estimations between polymorphisms and haplotype reconstruction were performed with Haploview version 4:1. Under different models adjusted by age, gender, body mass index, hypertension, diabetes mellitus, smoking habit, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels, rs43133 (OR=1.43, 95% CI: 1.05-1.94, P=0.022), and rs16900627 (OR=1.59, 95% CI: 1.00-2.54, Pdom=0.048 and OR=1.60, 95% CI: 1.05-2.54, Padd=0.028) were associated with increased risk of developing SA. Moreover, rs2293808, and rs431264 were associated with clinical or metabolic parameters in SA individuals and in healthy controls. The four polymorphisms were in high linkage disequilibrium and the GAAG haplotype was associated with increased risk of developing SA (OR=1.47, P=0.027). This study shows for the first time, that RIP2 polymorphisms are associated with increased risk of SA and with some clinical and metabolic parameters.
authors.affiliation: Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Posadas-Sánchez
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Ángeles-Martínez
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Nonanzit
authors.initials: N
authors.lastname: Pérez-Hernández
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Rodríguez-Pérez
authors.affiliation: Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Fabiola
authors.initials: F
authors.lastname: López-Bautista
authors.affiliation: Cardiovascular Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
authors.forename: Teresa
authors.initials: T
authors.lastname: Villarreal-Molina
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fragoso
authors.affiliation: Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Posadas-Romero
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: gvargas63@yahoo.com.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
mesh_terms: D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008297:Male; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000235:genetics*; D012307:Risk Factors
chemical_list: D008055:Lipids; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2
keywords: Inflammation; Polymorphisms; Receptor-interacting protein 2 (RIP2); Subclinical atherosclerosis