Functional polymorphisms of the fractalkine receptor gene and atherosclerosis risk factors in patients with coronary artery disease
BACKGROUND: Coronary artery disease (CAD) is the most cause of death in the world. CX3CR1 is a chemokine receptor which induces leukocyte adhesion and migration via attaching to fractalkine. The polymorphisms V249I and T280M affect receptor expression and function. In this study, we investigated the association between CX3CR1 polymorphisms and CAD.
METHODS: We studied 220 subjects referred to cardiovascular wards of Imam Khomeini hospital, in Ahvaz-Iran. Based on their angiography results,112 subjects had coronary artery stenos is (case group) and 108 had normal coronary arteries (control group). After collecting blood samples, polymorphic genotypes were determined by Taqman real-time polymerase chain reaction (RT-PCR) and data analysis was done by NCSS software.
RESULTS: The mean (standard deviation) age of the patient population was 60 (±9); 36.6% females. Among patients, the most prevalent genotype belonged to the wild type homozygous single nucleotide polymorphism (SNP) 249 (70%). The most common clinical manifestation was attributable to combined homozygous 11+11(SNP249+SNP280). The risk of CAD in women with the combined genotype 11+11 was four times higher than in other women. In the whole population, wild homozygous and heterozygous genotypes of SNP280 were protective against CAD (p<0.05).
CONCLUSIONS: As wild and mutant alleles of SNP280 are accompanied with reduced risk of CAD, it seems that changes in monocyte attachments in carriers of these alleles are the protective mechanisms against atherosclerosis, but as CAD is a multi-factorial disease, other genetic and environmental factors affect the genotype interaction of these polymorphisms with CAD.
Keywords: Atherosclerosis, CX3CR1 polymorphism, Coronary risk factor