Are Myocardial Infarction–Associated Single-Nucleotide Polymorphisms Associated With Ischemic Stroke?

Abstract

Background and Purpose Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Methods Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results Despite having power to detect odds ratio of 1.09–1.14 for overall IS and 1.20–1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.

Genetics of Ischemic Stroke in Young Adults

“…In this analysis, none of the myocardial infarction/CAD-associated single-nucleotide polymorphisms were associated with IS in young populations (<50-year old); associations with IS sub-types (eg, large artery stroke) were not investigated in this young population. 67 …”

Genome-Wide Analysis of Blood Pressure Variability and Ischemic Stroke

“…This is a common exploratory approach used to study candidate genes that maybe associated with different vascular disorders such as MI and stroke through their effect on shared risk factors such as hypertension, diabetes and smoking 29 . Our sample size provided sufficient power to detect modest effect sizes ranging from 1.1-1.4 for overall ischemic stroke but as with other studies, had reduced power for subtypes due to small sample size.…”

The APOE E4 Allele Confers Increased Risk of Ischemic Stroke Among Greek Carriers

“…Firstly, as ischemic stroke may be caused by occlusion (~80% of the cases) or hemorrhage (~20% of the cases) of cerebral blood vessels, several gene polymorphisms with a potential functional effect on blood coagulation proteins have been investigated in the last decade as potential risk factors for IS or CHD, with inconclusive results [28][29][30]. Similarly, a large number of published genome-wide association studies (GWAS) investigating thousands of single nucleotide polymorphisms (SNPs) across the human genome have failed to identify DNA sequence variants which, even when combined, are in a position to provide clinically useful and robust genotype-phenotype associations [26][27][28][29]. On the one hand, the results of these studies confirm the complex and multifactorial basis of cerebro-and cardiovascular disease in general, and more specifically of IS and CHD, while at the same time they exhibit considerable phenotypic variations in patient selection and study design.…”