A preliminary study about the association of ninjurin-2 gene polymorphisms with large artery atherosclerotic ischemic stroke and the influence of atherosclerosis vascular bed

Abstract

Objective To investigate the relationship between ninjurin-2 (NINJ2) gene polymorphisms and large artery atherosclerotic (LAA) ischemic stroke, and the role of genetic factors in atherosclerosis vascular bed. Methods Our study was composed of 286 LAA ischemic stroke patients classified by TOAST criteria and 298 healthy matched controls. Polymerase chain reaction-restriction fragment length polymorphism or sequence-based typing to analyze four tag SNPs of NINJ2 in a case-control study was used, respectively. Results Both the genotype distributions and allele frequencies of rs11833579, rs10849373 and rs12425791 showed significant differences between cases and controls. The A allele carriers (GA+AA) genotype had significantly higher LAA risk compared with the GG homozygotes （OR（95%CI）=1.491（1.026—2.168），1.598（1.101—2.320），1.515（1.050—2.187），P=0.036，0.014，0.026） in a logistic regression model after adjustment for the conventional risk factors for ischemic stroke. But there was no evidence for association of rs110683806 between cases and the controls. Further analysis revealed that the GA+AA genotype of rs11833579 had a higher frequency in the posterior circulation atherosclerotic. The A allele of rs12425791 had a higher frequency in the intracranial atherosclerosis. Seven common haplotypes were identified between the LAA and controls. Haplotype analysis revealed that the frequencies of rs11063806-rs10849373-rs11833579-rs12425791 A-A-G-G（0.215 vs 0.142）,G-G-A-G(0.214 vs 0.158） and G-G-G-A（0.192 vs 0.128） in LAA group were higher than controls （OR（95% CI）=1.649（1.216—2.238），1.440（1.069—1.940），1.607（1.168—2.209）；P=0.001，0.016，0.003）, whereas A-G-G-G（0.016 vs 0.043） and G-G-G-G（0.143 vs 0.334） haplotype might have the opposite effect （OR（95%CI）=0.354(0.165—0.761)，0.329（0.246—0.439）；P=0.006，0.000). Conclusions Our study revealed that NINJ2 gene polymorphisms may be useful in genetic risk factor for LAA ischemic stroke. rs11833579 and rs12425791 may affect the atherosclerosis vascular bed. Key words: Brain infarction; Atherosclerosis; Cell adhesion molecules, neuronal; Polymorphism, single nucleotide