Assocication Analysis Between SNP Rs556621and Ischemic Stroke In A Chinese Han Population

Strokes are one of the three most common causes of death and the major cause of adultchronic disability. A stroke is a sudden onset of cerebral blood circulation disruption.Once a stroke has occurred, most affected individuals suffer from disability, cognitivedysfunction and other complications and have a higher risk of death. In China, almost2million patients suffer from stroke per year. The number of stroke patients is about7millions at the present time and most of them are in varying degrees of loss of labor andliving abilities.The ischemic stroke(IS) accounts for60-70%of all strokes. It can be classified intothree main subtypes with known etiology, including large-artery atherosclerosis (LAA),cardiogenic embolism(CE) and small-artery occlusion (SAA). The ratios of these subtypesare17.3%,9.3%and30.9%, respectively.A recent genome-wide association study(GWAS) in patients with IS in the Australianpopulation demonstrated that a common single nucleotide polymorphism (SNP) onchromosome6p21.1, rs556621, was associated with ischemic strokes, especially largeartery atherosclerotic strokes (LAA). SNP rs556621lies within a small genomic regionthat contains BCL3and PBX3transcription factor–binding motifs. A number of predictedmicroRNAs (miRNAs) also lie in the vicinity of SNP rs556621, suggesting that variants inlinkage disequilibrium with rs556621could also potentially regulate gene expression.However this intresting association result has not been replicated in a non-Australianpopulation. Therefore, to study the association between SNP rs556621and ischemicstrokes in Chinese Han population is of great significance.The major goal of my thesis research is to assess whether SNP rs556621confers asignificant risk of strokes in the Chinese Han population. A case-control association studywith1129IS patients and1231controls without IS were genotyped for SNP rs556621using the High Resolution Melting (HRM) analysis combined with sequencing analysis.The relationship between SNP rs556621and ischemic stroke subtypes were also carriedout with339lacunar stroke patients and790non-lacunar infarction IS). No significantassociation was identified between SNP rs556621and ischemic strokes (P=0.246,OR=1.129[0.920-1.385]). SNP rs556621did not show significant association withlacunar strokes (P=0.142, OR=1.261[0.925-1.717]) and non-lacunar infarctionIS(P=0.626, OR=1.060[0.838-1.340]) in the Chinese Han population, either. I conclude that SNP rs556621does not confer risk of ischemic strokes in the Chinese Han population.Population differences, modifier genes, life style differences, and other environmentalfactors may be responsible for the ethnic differences in association as found here for theAustralian population and the Chinese Han population.