J Clin Neurol.  2013 Oct;9(4):223-230. 10.3988/jcn.2013.9.4.223.

MRAS Genetic Variation Is Associated with Atherothrombotic Stroke in the Han Chinese Population

• Liu H
• Huang XQ
• Yang M
• Ji XM
• Du X
• Zheng J

• KMID: 1980541
• DOI: http://doi.org/10.3988/jcn.2013.9.4.223

Abstract

BACKGROUND AND PURPOSE
Atherothrombotic cerebral infarction [atherothrombotic stroke (ATS)] shares common risk factors and pathophysiological mechanisms with coronary artery disease (CAD), and both diseases appear to have common susceptibility loci. The muscle RAS oncogene homolog gene (MRAS) has been identified as a susceptibility locus for CAD and is implicated in atherosclerosis. The aim of this study was to elucidate whether the single-nucleotide polymorphisms (SNPs) and haplotypes of MRAS are associated with increased risk of ATS in a population of Han Chinese.
METHODS
A case-controlled association study was conducted in which only patients with ATS (identified as a major subtype in the Korean modification of the Trial of Org 10172 in Acute Stroke Treatment classification) were enrolled. Subgroup analyses were carried out to determine whether the effect of the MRAS polymorphism was specific to age and gender among the subjects.
RESULTS
In total, 194 ATS and 186 control subjects were included in the present study. Two tagging SNPs were identified in MRAS (rs40593 and rs3755751). A multivariate regression analysis revealed a positive association between rs40593 and ATS under dominant and additive models after adjustment for covariates. Subgroup analyses revealed that there were no gender differences with respect to allele or genotype frequencies between the groups. The AG genotype for rs40593 (p=0.028), the CT genotype for rs3755751 (p=0.036), and G-allele carriers (AG plus GG) for rs40593 (p=0.015) exhibited a significant protective effect among those aged > or =45 years. For the haplotype analysis, ATS subjects aged > or =45 years had a higher frequency of the ACAC haplotype (76.0%) than the controls (68.1%; p<0.05); that haplotype was associated with an increased risk of ATS.
CONCLUSIONS
The obtained data suggest a positive association between MRAS and ATS among the Han Chinese. Further studies should be performed with larger sample and among different ethnic populations, and gene-gene or gene-environment interactions should be considered.

Keyword

ischemic stroke; atherothrombotic stroke; single-nucleotide polymorphism; haplotype; genetic variation

MeSH Terms

Alleles
Asian Continental Ancestry Group*
Atherosclerosis
Case-Control Studies
Cerebral Infarction
Chondroitin Sulfates
Coronary Artery Disease
Dermatan Sulfate
Gene-Environment Interaction
Genes, ras
Genetic Variation*
Genotype
Haplotypes
Heparitin Sulfate
Humans
Muscles
Polymorphism, Single Nucleotide
Risk Factors
Stroke*
Chondroitin Sulfates
Dermatan Sulfate
Heparitin Sulfate

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