Association studies of candidate single-nucleotide polymorphisms with Symptomatic Intracranial Atherosclerotic Stenosis in a Chinese Han population

Abstract

Background: Genetic factors underlying predisposition to Symptomatic Intracranial Atherosclerotic Stenosis (sICAS) remain unknown, the purpose of the present study was to identify genetic variants that confer susceptibility to sICAS in a Chinese Han population. Methods: The study population comprised of 379 Chinese individuals, including 193 patients with sICAS and 186 unrelated healthy controls. A total of 96 polymorphisms selected by genome-wide association or candidate-gene association studies of atherosclerosis and atherosclerotic diseases were examined in the present study with the use of Illumina VeraCode technology. Statistical analyses were performed with PLINK and SPSS software, and each genotype was assessed according to dominant, recessive, and additive genetic models. Results: Comparisons between subjects with sICAS and controls revealed that rs3798220 of the lipoprotein(a) gene (LPA) and rs9818870 of the muscle RAS oncogene homolog gene (MRAS) were significantly (P<0.0005, Bonferroni correction) associated with the prevalence of sICAS. Comparisons of genotypes in three genetic models (dominant, recessive and additive models) between groups showed that rs3798220 (LPA) was associated with sICAS in the dominant model (P=0.000005, OR=2.629, 95% CI=1.735-3.985) and additive model (P=0.000005, OR=2.293, 95% CI=1.605-3.276),while rs9818870 (MRAS) was associated with sICAS in the additive model (P=0.000464, OR=3.245, 95% CI=1.679-6.272). Furthermore, logistic regression analysis showed that the genotype distribution of rs3798220 (LPA) was significantly associated with sICAS, with its minor C allele elevating sICAS risk (P=0.00002, dominant model, OR=3.951, 95% CI=2.100-7.434 and P=0.000053, additive model, OR=2.916, 95% CI=1.736-4.899). While rs9818870 (MRAS) showed no such significance (P>0.0005). Conclusion: LPA rs3798220 might be susceptibility loci for sICAS in Chinese Han individuals. Keywords: Symptomatic Intracranial Atherosclerotic Stenosis; risk factors; candidate gene; SNP.