Monocyte chemoattractant protein-1 gene (MCP-1) polymorphisms are associated with risk of premature coronary artery disease in Mexican patients from the Genetics of Atherosclerotic Disease (GEA) study.
The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, progression, and destabilization of atheromatous plaques and plays an essential role in postinfarction remodeling. The aim of the present study was to evaluate the role of MCP-1 gene polymorphisms as susceptibility markers for premature coronary artery disease (CAD) and cardiovascular risk factors in the Mexican population. Four MCP-1 gene polymorphisms (rs1024611, rs2857654, rs3760396, and rs1024610) were genotyped by 5' exonuclease TaqMan assays in a group of 1072 patients with premature CAD, and 1082 healthy unrelated controls (with negative calcium score by computed tomography) seeking for associations with premature CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. MCP-1 polymorphism frequencies were similar in premature CAD patients and healthy controls. When the analysis included only those premature CAD patients without type 2 diabetes mellitus (T2DM), the rs1024610 polymorphism was associated with increased risk of developing premature CAD under dominant and additive models adjusted by age and gender (OR=1.33, Pdom=0.040 and OR=1.34, Padd=0.027). The effect of the MCP-1 polymorphisms on various metabolic cardiovascular risk factors and metabolic parameters was explored separately in controls, and premature CAD. In this analysis adjusted by age and gender, the rs3760396 CC genotype was associated with low levels of gamma-glutamyl transpeptidase (P=0.002), whereas, the rs1024610 TT genotype was associated with decreased risk of T2DM (P=0.035) in premature CAD patients. One haplotype (CATG) was associated with increased risk of developing premature CAD (OR=1.44, P=0.0019). In summary, in our study, the rs1024610 polymorphism was associated with increased risk of developing premature CAD only in those patients without T2DM. The four MCP-1 polymorphisms were in high linkage disequilibrium and one haplotype was significantly associated with risk of developing premature CAD.
Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: jabojangeles@yahoo.com.mx.
Javier
J
Angeles-Martínez
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: rossy_posadas_s@yahoo.it.
Rosalinda
R
Posadas-Sánchez
Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: edalvaleo@yahoo.com.
Edith
E
Álvarez-León
Cardiovascular Genomics Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico. Electronic address: mtfvillarreal@yahoo.com.mx.
Teresa
T
Villarreal-Molina
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: gccardosos@yahoo.com.
Guillermo
G
Cardoso-Saldaña
Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: mfragoso1275@yahoo.com.mx.
José Manuel
JM
Fragoso
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: gaboyk2@gmail.com.
Juan Gabriel
JG
Juárez-Rojas
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: aidaxm@yahoo.com.
Aida
A
Medina-Urrutia
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: cposadasr@yahoo.com.
Carlos
C
Posadas-Romero
Departments of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico. Electronic address: gvargas63@yahoo.com.
Gilberto
G
Vargas-Alarcón
D000483:Alleles; D015415:Biomarkers; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D014057:Tomography, X-Ray Computed
D015415:Biomarkers; D018932:Chemokine CCL2
Coronary artery disease; Haplotypes; Monocyte chemoattractant protein; Polymorphisms; Susceptibility markers