The Association Between C-reactive Protein Sigle Nucleotide Polymorphisms Andd Ischemic Strocke

Background:Ischemic stroke (IS) is a multi-factorial disease, which is related to both the genetic and environmental factors.Gene-gene and gene-environmental interaction makes great contribution to the risk of IS. With the advance of Human Genome Project and The International HapMap Project, it has become more and more popular in medical fields to clarify the pathogenesis of IS at genetic level, especially IS. In recent years, studies have suggested inflammatory mechanisms are involved in the pathology of atherosclerosis. Among them, C-reactive protein (C-reactive protein, CRP) has important clinical value. However, reports are extremely rare presently on the association between the CRP single nucleotide polymorphisms (SNP) and IS, and the interaction between the gene polymorphisms and environmental factors.Objective:(1) To investigate the association between the rs2808632G>T and rs1800947G>C polymorphisms in CRP gene and the concentration of serum high sensitivity CRP (hs-CRP) and IS.(2) To explore and assess the possible interaction effects between the gene polymorphisms and environmental factors.Methods:Case-control study method was used to determine the possible the association between CRP gene and IS. A total of 94 patients with with IS and 98 healthy individuals of Chinese origin were were recruited in this study. The cases and controls were interviewed using the same questionnaire, and the blood samples were drawn in terms of the same conditions and standards.Gene polymorphisms were determined by using polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) and DNA sequence. Univariate test and multiple logistic regression models were used to explore the association between the SNPs and IS. Additionally, the interaction between SNPs and environmental risk factors were assessed by MDR1.1.0.Results:(1) The rs1800947G>C genotype distributions was not consistent with the Hardy-Weinberg equilibrium, which was removed from further analysis.(2) No significant differences were observed in rs2808632G>T genotype distributions between IS patients and controls in the additive model (GG vs GT vs TT, P=0.11).The rs2808632G>T genotype frequencies in the recessive model (GT+TT vs TT) differed significantly between IS patients and controls (P=0.264). However, a trend toward a higher genotype distributions of GG+GT was observed in cases with respect to controls with reaching a statistical significance (P=0.042). Furthermore, rs2808632G was associated with IS(34.04% vs 20.41%, P=0.03).(3) The serum level of hs-CRP of GG+GT genotype of CRP rs2808632 gene cite in the control and IS group were both higher than of TT genetype, but the difference was not significant(P>0.05).(4) After adjustment for age, gender, and frequencies of hypertension, diabetes mellitus, and smoking, rs2808632GG+GT was not associated with IS(OR 1.918,95%CI 0.944～3.898).(5) The interactions were found between rs2808632G>T polymorphism, smoking and Coronary heart disease.Conclusion:(1) No definite conclusion could be reached regarding the involvement of the rs2808632G>T polymorphism of CRP and the serum level of hs-CRP, whereas rs2808632G>T polymorphism might contribute to an increased risk of IS.(2) rs2808632G>T polymorphism, smoking and Coronary heart disease have a possible interaction on the presence of IS, which may result in a possible effect on stroke risk.