Abstract
Ischemic stroke is a multifactorial disease with strong genetic elements. The purpose of this case-control study was to find relationships between apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR) genotypes and atherosclerosis of the extracranial internal carotid and intracranial arteries in the Thai population. Patients aged >45 years with significant intracranial stenosis (IC group) or extracranial carotid artery stenosis (EC group) diagnosed by duplex ultrasound and/or computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were studied. The control group comprised volunteers with no history of stroke and no evidence of significant cervicocerebral artery stenosis by ultrasound. Genomic DNA was extracted and genotyped for APOE isoforms, ACE insertion/deletion (I/D) polymorphism, and MTHFR C677T polymorphisms. There were 141 cases (83 in the IC group and 58 in the EC group) and 167 controls. The APOE ε3/ε4 genotype and APOE ε4 allele were significantly associated with extracranial carotid artery stenosis (odds ratio, 2.55; 95% confidence interval, 1.07-6.05 and odds ratio, 2.85; 95% confidence interval, 1.35-5.99, respectively). These associations were not observed in patients with intracranial atherosclerosis. There was no significant association between ACE and MTHFR polymorphisms and stenosis at any site. In a multivariate model, sex, diabetes mellitus, hypertension, ischemic heart disease, and APOE ε4 allele remained predictive of extracranial atherosclerosis. In our Thai population, the ε4 allele in the APOE gene contributes to the genetic susceptibility of extracranial internal carotid atherosclerosis. The low prevalence of extracranial carotid stenosis in this population might result from low frequencies of the APOE ε4 allele.
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