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

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.

Caracterización del infarto cerebral de etiología aterotrombótica, del territorio carotídeo según tomografía computarizada / Characterization of atherothrombotic stroke, in carotid region as computed tomography

Introducción: la causa más frecuente de enfermedad cerebrovascular isquémica en Cuba es el infarto cerebral de etiología aterotrombótica, que a su vez es más frecuente en el territorio anterior del encéfalo. Objetivo: caracterizar el infarto cerebral aterotrombótico reciente del territorio carotídeo, según la tomografía computarizada. Métodos: estudio descriptivo y transversal en 42 pacientes con diagnóstico clínico de infarto cerebral aterotrombótico de territorio carotídeo, a los que se les realizó tomografía de cráneo. Resultados: la presencia de infarto cerebral de origen aterotrombótico del territorio carotídeo se incrementó con la edad del paciente, alcanzó su pico máximo en los hipertensos mayores de 70 años, con mayor frecuencia en el sexo masculino. El territorio vascular más afectado fue el de la arteria cerebral media en 38 (90,5 %) enfermos, en 23 (54,7 %) pacientes hubo infartos medianos y se observó con mayor frecuencia, 24 (57,2 %) sujetos, la ausencia de infarto antiguo en el territorio anterior del cerebro. Conclusiones: el infarto cerebral aterotrombótico reciente, del territorio carotídeo, se caracteriza por la presencia de infartos medianos que afectan con mayoría casi exclusiva el territorio de la arteria cerebral media con ausencia de la enfermedad cerebrovascular antigua asociada.

Introduction: the most common cause of ischemic stroke in Cuba is atherothrombotic stroke, which, in turn, is more common in the former region of the brain. Objective: to characterize the recent atherothrombotic stroke in the carotid region, according to CT scan. Methods: a descriptive study in 42 patients with clinical diagnosis of atherothrombotic stroke in the carotid region, who underwent cranial CT. Results: the presence of atherothrombotic stroke in the carotid region increased with age. It peaked in hypertensive patients older than 70, and it is much frequently in males. The middle cerebral artery was the most affected in the vascular region in 38 (90.5 %) patients, 23 (54.7 %) patients had middle heart attacks, the absence of previous infarction in the brain anterior region was much frequently observed in 24 (57.2 %) subjects. Conclusions: the recent atherothrombotic stroke in the carotid region is characterized by the presence of middle heart attacks affecting almost exclusively the majority the middle cerebral artery region with absence of previous cerebrovascular disease associated.