Combinations of Polymorphic Markers of Chemokine Genes, Their Receptors and Acute Phase Protein Genes As Potential Predictors of Coronary Heart Diseases.

Atherosclerosis, the main factor in the development of coronary heart diseases (CHD), is an inflammatory response to endothelial layer damage in the arterial bed. We have analyzed the association between CHD and the polymorphic markers of genes that control the synthesis of proteins involved in the processes of adhesion and chemotaxis of immunocompetent cells: rs1024611 (-2518A>G, CCL2 gene), rs1799864 (V64I, CCR2 gene), rs3732378 (T280M, CX3CR1 gene), rs1136743 (A70V, SAA1 gene), and rs1205 (2042C>T, CRP gene) in 217 patients with CHD and 250 controls. Using the Monte Carlo method and Markov chains (APSampler), we revealed a combination of alleles/genotypes associated with both a reduced and increased risk of CHD. The most significant alleles/genotypes areSAA1*T/T+CRP*C+CX3CR1*G/A (P perm = 0.0056, OR = 0.07 95%CI 0.009-0.55), SAA1*T+CRP*T+CCR2*G/A+CX3CR1*G (P perm = 0.0063, OR = 14.58 95%CI 1.88-113.04), SAA1*T+CCR2*A+CCL2* G/G (P perm = 0.0351, OR = 10.77 95%CI 1.35-85.74).

[Association of polymorphic markers of chemokine genes, their receptors, and CD14 gene with coronary atherosclerosis].

Atherosclerosis represents an inflammatory response to the disturbance of the endothelial layer in the arterial bloodstream. In the present study, an analysis of associations of polymorphic markers for the genes controlling synthesis of proteins involved in atherosclerosis pathogenesis in coronary atherosclerosis (CA) patients (217 subjects) and in a control group (250 subjects) was conducted. The following genes were examined: rs991804 (CCL2 gene), rs1126579 (CXCR2 gene), rs4074 (CXCL1 gene), rs4073 (CXCL8 gene), rs333 (CCR5 gene), rs2471859 (CXCR4 gene), rs1801157 (CXCL12 gene), and rs2569190 (CD14 gene). Using the Monte Carlo and Markov chain (APSampler) method, allele/genotype combinations associated with both low and high CA risk were revealed. The most important findings included the following: CXCR4*T/T + CCL2*C + CCR5*I/I (P perm = 1 × 10­6, OR = 0.44, 95% CI 0.3­0.63), CXCR2*C + CD14*C + CXCL12*G + CCL2*C + CCR5*D (P perm = 4 × 10­6, OR = 5.78, 95% CI 2.34­14.28), CD14*C + CCL2*C/C + CCR5*D (P perm = 6.3 × 10­6, OR = 5.81, 95% CI 2.17­15.56), CXCL8*A + CXCR2*C + CD14*T + CXCR4*C (P perm = 0.01, OR = 3.21, 95% CI 1.63­6.31).