Association Of CCL11 And COL4A2 Gene Polymorphism With Lacunar Stroke In Xinjiang Han Populations

Objective: To investigate the risk factors of lacunar stroke,the association of CCL11 and COL4A2 gene polymorphism with lacunar stroke,and the association of COL4A2 mRNA expression with lacunar stroke in Xinjiang Han populations.Methods: There were 406 Han lacunar stroke patients and 425 controls for the study.Clinical data were collected,and the genetic DNA was extracted from all subjects.The improved multiple ligase detection reaction(iMLDR)method was used to analyze the genotypes of SNPs in the CCL11 and COL4A2 gene.A total of 50 patients with lacunar stroke and 50 controls were selected from all subjects.RNA was extracted from peripheral blood lymphocytes.The lever of mRNA expression was detected by Real-time quantitative PCR.SPSS 17.0 was used for data analysis.The statistical methods included chi-square test,multiple logistic regression,and Mann-WhitneyU-test.Results:(1)Hypertension(OR=1.869,95%CI=1.401-2.494,P=0.000),diabetes(OR=3.163,95%CI=2.198-4.552,P=0.000)were the independent risk factors for lacunar stroke.The age≥60 years(OR=2.941,95%CI=1.766-4.897,P=0.000),hypertension(OR=11.281,95%CI=6.700-18.995,P=0.000),diabetes(OR=4.201,95%CI=2.330-7.574,P=0.000)were the independent risk factors for lacunar stroke with leukoaraiosis.(2)We found the GG genotype of rs4795895 in CCL11 gene was significantly associated with increased risk of lacunar stroke(adjusted OR=1.676,95%CI=1.117-2.515,P=0.013).The GG of rs3803230(adjusted OR=1.303,95%CI=1.146-1.480,P=0.000)and the GA/AA genotype of rs76425569 were associated with a significant increase in risk of lacunar stroke(adjusted OR=1.744,95%CI=1.306-2.329,P=0.000).Age stratification analyses showed that rs3803230 of COL4A2 gene was significantly associated with lacunar stroke in the groups of age<60 years and age ≥60 years(all P<0.05).The rs76425569 of COL4A2 gene was significantly associated with lacunar stroke in the group of age<60 years(P<0.05).The CC genotype of rs9521733(rs9515199)or AA genotype of rs9521732 were associated with a significant increase in risk of lacunar stroke in the group of age≥60 years(adjusted OR=1.950,95%CI=1.222-3.112,P=0.005).Sex stratification showed that rs76425569 of COL4A2 gene was significantly associated with lacunar stroke in the male group and female group(all P<0.05).The rs4795895 of CCL11 gene and rs3803230 of COL4A2 gene were significantly associated with lacunar stroke in the male group(all P<0.05).The CT/TT genotype of rs4103 in COL4A2 gene was associated with a significant increase in risk of lacunar stroke in the male group(adjusted OR=1.531,95%CI=1.193-1.964,P=0.001).Hypertension stratification analyses showed that rs76425569 of COL4A2 gene was significantly associated with lacunar stroke in the hypertensive group and non-hypertensive group(all P<0.05).The rs4795895 of CCL11 gene and rs3803230 of COL4A2 gene were significantly associated with lacunar stroke in the non-hypertensive group(all P<0.05).The TT genotype of rs1860184 in CCL11gene(adjusted OR=2.440,95%CI=1.550-3.840,P=0.000)and the TT genotype of rs4103 in COL4A2 gene were associated with a significant increase in risk of lacunar stroke in the non-hypertensive group(adjusted OR=1.355,95%CI=1.152-1.594,P=0.000).(3)There was no significant difference in the level of mRNA expression of COL4A2 gene between the case group and the control group(P>0.05).There were no significant differences in the association between genetypes of COL4A2(rs3803230,rs76425569)and mRNA expression(all P>0.05).Conclusion:(1)Hypertension and diabetes were independently associated with lacunar stroke in Xinjiang Han populations.The age≥60 years,hypertension,diabetes were independently related to lacunar stroke with leukoaraiosis.(2)The rs4795895 of the CCL11 gene might be associated with lacunar stroke,particularly in the male group and non-hypertensive group.The rs1860184 of the CCL11 gene was associated with a higher risk of lacunar stroke in the non-hypertensive group.The rs3803230 of the COL4A2 gene might be associated with lacunar stroke,particularly in the male group and non-hypertensive group.The rs76425569 of the COL4A2 gene might be associated with lacunar stroke,particularly in the group of age ≥60 years.The rs9521733(rs9515199)or rs9521732 of the COL4A2 gene were associated with a higher risk of lacunar stroke in the group of age ≥60 years.The rs4103 of the COL4A2 gene was associated with a higher risk of lacunar stroke in the male group and non-hypertensive group.(3)The expression level of COL4A2 gene mRNA might not be associated with lacunar stroke.No association was found between the COL4A2(rs3803230,rs76425569)and mRNA expression.