ABSTRACT
Noncardioembolic stroke and coronary heart disease (CHD) may share genetic predispositions. We tested the hypothesis that genetic variants which are associated with risk of CHD would also be associated with risk of noncardioembolic stroke in 562 cases from the Vienna Stroke Registry and 815 controls. We selected 6 gene variants that had been consistently associated with risk of CHD in 3 studies, including the Atherosclerosis Risk in Communities study, and found that 4 of these gene variants were also associated with risk of noncardioembolic stroke. The odds ratios for noncardioembolic stroke were 1.31 (90% CI 1.07-1.60) for rs3900940 in MYH15, 1.24 (90% CI 1.01-1.5) for rs20455 in KIF6, 1.21 (90% CI 0.99-1.49) for rs1010 in VAMP8, and 1.20 (90% CI 0.95-1.50) for rs10757274 on chromosome 9p21.
Subject(s)
Coronary Disease/genetics , Polymorphism, Genetic/genetics , Stroke/genetics , Aged , Atherosclerosis/epidemiology , Austria/epidemiology , Female , Humans , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide/genetics , Registries , Risk , Risk FactorsABSTRACT
OBJECTIVE: Identify gene variants associated with early-onset myocardial infarction (MI). METHODS AND RESULTS: We tested 11 647 single-nucleotide polymorphisms (SNPs) for association with early-onset MI in a case-control study (study 1 200 cases, 262 controls). To reduce the number of false positives among the 666 SNPs that were nominally associated with early-onset MI (P<0.05) in study 1, we tested these SNPs in study 2 (434 cases, 504 controls). We found that 8 of the 666 SNPs were associated with early-onset MI in study 2 (P<0.05) and had the same risk alleles as in study 1. These 8 SNPs were then tested for association with early-onset MI in study 3 (187 cases, 434 controls). We found that a VAMP8 variant (P = 0.025; odds ratio [OR], 1.75; CI, 1.17 to 2.62) and an HNRPUL1 variant (P = 0.0043; OR, 1.92; CI, 1.28 to 2.86) were associated with early-onset MI (nominal P<0.05; false discovery rate <10%) and had the same risk alleles in all 3 studies. CONCLUSIONS: Variants in 2 genes were associated with early-onset MI: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. The identification of these variants could improve understanding of disease mechanisms and suggest novel drug targets.
