Genetic Variation of the Kalirin Gene is Associated with ICAS in the Chinese Population

Abstract

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic stroke (IS), especially in recurrent patients. Several studies have demonstrated an intimate association between the genetic mutation of the KALRN gene and IS. The main aim of this study was to clarify the relationship between three single nucleotide polymorphisms (SNPs) of KALRN and ICAS in a northern Chinese population and further explore the underlining mechanism. The relationship between each SNP and ICAS and the related components were examined in five models (co-dominant, dominant, recessive, heterozygous, and additive). Multivariate logistic regression models were applied and adjusted for 10,000 permutation tests. Haplotype regression analysis was performed to determine the associations between haplotypes and the severity of ICAS. qRT-PCR was used to confirm the mRNA level of Kalirin. SNP rs6438833 of the Kalirin gene in the additive model was associated with ICAS (OR = 1.642, 95%CI: 1.129-2.388, P_Dom = 0.048). After performing 10,000 permutations, the result showed a trend toward statistical significance (Pper = 0.048). Haplotypes of the KALRN gene were not significantly associated with ICAS (global significance, p = 0.090). qRT-PCR showed that the expression of KALRN 9 in IS patients was almost threefold the control group (p < 0.0005). SNPs of the KALRN gene are associated with ICAS in the northern Chinese population.

Keywords: Intracranial atherosclerotic stenosis; Ischemic stroke; KALRN; SNP.