Genetic variation at the chemokine receptors CCR5/CCR2 in myocardial infarction.
Our objective was to examine the association between myocardial infarction (MI) and two DNA-polymorphisms at the proinflammatory chemokine receptors CCR2 (I64V) and CCR5 (32 bp deletion, (Delta)ccr5), defining if these polymorphisms influence the age for the onset of MI. A total of 214 patients with an age at the first MI episode <55 years, 96 patients that suffered the first MI episode when older than 60 years, and 360 population controls were polymerase chain reaction genotyped for the CCR2-V64I and CCR5-Delta32/wt polymorphisms. Patients and controls were male from the same Caucasian population (Asturias, northern Spain). The frequency of the Deltaccr5 allele was significantly higher in controls compared to patients <55 years (P = 0.004), or in patients >60 years compared to patients <55 years (P = 0.002). Taking the patients >60 years as the reference group, non-carriers of the (Delta)ccr5-allele would have a three-fold higher risk of suffering an episode of MI at <55 years of age (OR = 3.06; 95% CI = 1.46-6.42). Gene and genotype frequencies for the CCR2 polymorphism did not differ between patients <55 years and controls or patients >60 years. Our data suggest that the variation at the CCR5 gene could modulate the age at the onset of MI. Patients carrying the (Delta)ccr5-allele would be protected against an early episode of MI. CCR5 and the CCR5-ligands are expressed by cells in the arteriosclerotic plaque. Thus, the protective role of (Delta)ccr5 could be a consequence of an attenuated inflammatory response, that would determine a slower progression of the arteriosclerotic lesion among (Delta)ccr5-carriers. Our work suggests that the pharmacological blockade of CCR5 could be a valuable therapy in the treatment of MI.
González
P
P
Genética Molecular-Instituto Reina Sofía de Investigación Nefrológica, Spain.
Alvarez
R
R
Batalla
A
A
Reguero
J R
JR
Alvarez
V
V
Astudillo
A
A
Cubero
G I
GI
Cortina
A
A
Coto
E
E
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*
C515334:CCR2 protein, human; D017931:DNA Primers; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine