Research On The Association Between CARD8 Polymorphism And Large-artery Atherosclerosis Stroke In Chinese Population

Background:Stroke is the leading three causes of mortality and disability worldwide.To study the pathogenesis of stroke,to find the risk factors of stroke and to realize the secondary prevention of stroke can reduce the economic and social burden brought by stroke.The single nucleotide polymorphism rs2043211 of CARD8 was significantly associated with the susceptibility of ischemic disease and inflammatory diseases.This study aimed to investigate the correlation between rs2043211 and LAA（large-artery atherosclerosis）stroke in Chinese and to explain its possible mechanism.Methods:A total of 716 patients with LAA stroke and 1088 controls were included in the case-control study.Genetic models were constructed to evaluate the relationship between rs2043211 and LAA stroke risk by OR with 95%CIs,and stratified analysis and interaction analysis were performed.In addition,we studied whether rs2043211 affects the age of onset in LAA stroke patients.The plasma secretory CARD8 level was measured in another 111 LAA stroke patients. Combining with the results of bioinformatics analysis and our research,we tried to predict the possible mechanism of that how rs2043211 affects the risk of LAA stroke.Results:Compared with the AA+AT genotype,the individuals’TT genotype showed a higher risk of LAA stroke（OR=1.35,95%CI:1.03-1.77,P=0.029）.The risk remained significant among women,hypertensive patients,and non-diabetic patients.In the interaction analysis,compared to the non-hypertensive participants with the wild homozygote type AA,the hypertensive participants with the AT+TT homozygote had 3.27-fold increased risk（OR=3.27,95%CI:2.33-4.60）.Among the affected population,the age-related cumulative non-morbidity frequency of different genotypes was statistically different（P=0.041）.The plasma CARD8 level in patients of AA genotype was lower than that of AT+TT genotype（P<0.001）.Further bioinformatics analysis showed that rs2043211 has a significant impact on the secondary structure,transcription and translation functions of CARD8 mRNA(eQTL P=9.8×10^-198).Conclusions:The SNP rs2043211 T allele is associated with the risk of LAA stroke in the Chinese Han population,indicates an earlier age of onset,and may be a new biomarker of the disease.