| Background: Large artery atherosclerosis(LAA)stroke is the most common ischemic stroke(IS)subtype,and microemboli are clinically important for indicating increased risk of IS.Inflammation is involved in the pathogenesis of atherosclerosis,and lymphocyte tyrosine phosphatase(LYP),which is encoded by the protein tyrosine phosphatase nonreceptor 22(PTPN22)gene,plays an important role in the inflammatory response.The aim of this study is to investigate the relationship between PTPN22 gene polymorphism and susceptibility to LAA and microembolic signals(MES)in the Han Chinese population.Methods: Three loci of the PTPN22 gene(rs2476599,rs1217414 and rs2488457)were analyzed in 364 LAA patients and 369 control subjects.All patients were subjected to microembolism monitoring by using transcranial Doppler(TCD)ultrasound.Depending on the presence of MES,the patients were divided into MES-negative and MES-positive subgroups.A genotyping determination was performed using the Taq Man assay.All statistical analyses were performed using the SPSS 20.0 software.Results: The frequencies of GG,CG and CC genotypes at rs2488457 locus were 19.8%,45.9% and 34.3%,respectively,in the LAA group,and 10.8%,43.6% and 45.5% in the control group,respectively.The allele frequencies of G and C in the LAA group were42.7% and 57.3%,respectively,and those of control group were 32.7% and 62.3%,respectively.The GG genotype of rs2488457 increased the risk of LAA(OR = 2.419,95% CI 1.542-3.796,P < 0.001),and individuals with G allele had 1.538 times the risk of LAA as those with C allele(OR = 1.538,95% CI 1.243-1.903,P < 0.001).After Logistic regression was used to correct for confounding factors,the frequencies of GG genotype and G allele were still statistically significant between two groups(OR = 2.275,95% CI1.395-3.709,P = 0.001;OR = 1.456,95% CI 1.156-1.833,P = 0.001).In the LAA group,microembolic signal(MES)was observed in 95 patients,and 269 patients did not presented with microembolic signals.The frequencies of GG,CG and CC genotypes at rs2488457 locus were 29.5%,44.2% and 26.3%,respectively,in the MES(+)group,and16.4%,46.5% and 37.2%,respectively,in the MES(-)group.The allele frequencies of G and C in the MES(+)group were 51.6%,48.4%,and those of control group were 39.6%,60.4% respectively.The GG genotype of rs2488457 increased the risk of MES(OR =2.545,95% CI 1.335-4.854,P = 0.004),and individuals with G allele had 1.625 times the risk of MES as those with C allele(OR = 1.625,95% CI 1.165-2.267,P = 0.004).After Logistic regression was used to correct for confounding factors,the frequencies of GG genotype and G allele were still statistically significant between two groups(OR = 2.591,95% CI 1.339-5.011,P = 0.005;OR = 1.652,95% CI 1.177-2.319,P = 0.004).However,two polymorphisms of rs2476599 and rs1217414 were not found to be associated with LAA(OR = 1.153,95% CI 0.740-1.797,P = 0.529;OR = 1.259,95% CI 0.867-1.827,P =0.225)and MES(OR = 1.066,95% CI 0.537-2.115,P = 0.855;OR = 1.134,95% CI0.649-1.984,P = 0.659).After adjusting for confounding factors,it was still not found to be correlated with LAA and MES(P > 0.05).Linkage imbalance analysis of three loci of PTPN22 gene showed that there was linkage disequilibrium among the three loci.Haplotype analysis showed that the frequency of G-C-C haplotype in the control group was higher than that in the LAA group(OR = 0.682,95% CI 0.547-0.850,P = 0.001),and the frequency of G-T-G haplotype in the LAA group was higher than that in the control group(OR = 2.778,95% CI 1.631-4.731,P < 0.001).Conclusion: PTPN22 rs2488457 is likely to be associated with the occurrence of LAA and MES in the Han Chinese population,and the G allele is likely a risk factor for LAA and MES.G-T-G haplotype may increase the susceptibility to LAA,while G-C-C haplotype may reduce the risk of LAA. |
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