Association Of Polymorphisms In DNA Repair System-related Genes With Susceptibility And Short-term Recovery Of Ischemic Stroke In Southern Chinese Han Population

Ischemic stroke,a main type of stroke,is a heterogeneousdisease,whose risk and clinical outcomes are influenced by multiple factors,including environmental and genetic factors.Thus far,there are two kinds of studies related to the genetic factors of ischemic stroke.The first one referred to the genes associated with the susceptibility of ischemic stroke and the other referred to the genes associated with the neural impairment and functional outcome of ischemic stroke.To our knowledge,limited information is avaible on the the relationship of genetic varients to the functional outcome of ischemic stroke,especially using detailed functional instruments.DNA repair system can fixbase lesions caused by oxidative damage,thus to maintain the integrity of the genome and normal functions of the cell.We hypothesizedgenes related to DNA repair pathway play aimportant role in ischemic stroke.This study evaluated how singlenucleotide polymorphisms(SNPs)of DNA repair system impact susceptibility and short-term recoveryof ischemic stroke.In Part ?,the association of polymorphisms of XRCC1 rs25487,NEIL1rs4462560 and NEIL3rs12645561 with susceptibility of ischemic stroke was examined in a Southern Han population in China.The results indicated that none of the SNPs showed a significant deviation from HWE in the controls(P= 0.247,0.530 and 0.231 for rs25487,rs12645561 and rs4462560,respectively).Only the SNP rs25487 showed asignificantly different distribution between the patient and control group.There were no significantdifferences observed in the other two SNPs.After being adjusted for age,sex,smoking,drinking,diabetes,hypertension,and total cholesterol,logistic regression analysis indicated that XRCC1 rs25487variant genotypes had significantly reduced IS risk(dominant model:OR=0.53,95%CI=0.36-0.79,P=0.002).This decreased risk remained significant after Bonferroni correction.In conclusion,our results suggested that genetic variants in base excision repair pathway of DNA repair system had influence on ischemic stroke susceptibility.In Part ?,this study evaluated the relationship between polymorphisms of XRCC1 rs25487,NEIL1rs4462560 and NEIL3rs12645561 and severity,short-term recovery and functional outcomes of ischemic stroke.After being adjusted for age and sex,logisticregression analysis showed that patients harboring the rs25487 AG/AA genotype had a milder initialstroke(dominant model:OR=0.57,95%CI=0.33-0.98,P=0.043),and also showed a better short-termrecovery(dominant model:OR=0.57,95%CI=0.35-0.92,P=0.022).The relationship of the XRCC1 rs25487 variant to the short-term functional outcome was nextanalyzed.Considering the few subjects with the AA genotype,we combined the AG and AA genotypesas one group.The t-test analysis of AFIM scores showed no significantdifference between the AG/AA group and the GG group(for AG/AA group,median:7,IQR=0-15;for GG group,median:9,IQR=0-14;P=0.798).In conclusion,patients carrying the rs25487 variant genotype had a milder acute severity and a better short-term recovery.