Abstract TMP50: A Polymorphism in HDAC9 was Associated with Large Vessel Stroke in the Vienna and German Stroke Studies
Introduction The International Stroke Genetics Consortium (ISGC) and the Wellcome Trust Case Control Consortium 2 (WTCCC2) performed a large genome wide association study of ischemic stroke and its subtypes (large vessel stroke (LVD), small vessel stroke (SVD), cardioembolic stroke (CE)), and identified a polymorphism in HDAC9 (rs11984041) associated with the LVD subtype of ischemic stroke.
Hypothesis We assessed the hypothesis that rs11984041 is associated with LVD in two additional studies.
Methods The genotype of rs11984041 was determined for participants of the Vienna Study (815 controls, 122 LVD, 165 SVD, 202 CE) and of the German Study (1040 controls, 495 LVD, 230 SVD, 462 CE). The association of rs11984041 with LVD was assessed by logistic regression. Heterogeneity of the effect of rs11984041 on LVD, CE or SVD was assessed by testing the equality of the corresponding regression coefficients from a multinomial logistic regression model.
Results Carriers of the minor (T) allele of rs11984041 (23.3% of LVD cases and 17.4% of controls), compared with noncarriers, had increased risk for LVD: the odds ratios (OR) were 1.92 (95%CI 1.25-2.96) for the Vienna Study and 1.33 (95%CI 1.02-1.74) for the German Study. Adjusting for covariates including sex, age, diabetes, and hypertension did not materially change the ORs. Heterogeneity of the effects of rs11984041 on LVD vs CE was significant in the Vienna Study (p = 0.009) and in the German Study (p = 0.005). Heterogeneity of the effects of rs11984041 on LVD vs SVD trended toward significance in the Vienna Study (p = 0.088) and was significant in the German Study (p = 0.047). Adjusting for covariates did not materially change the heterogeneity test p values.
Conclusions The HDAC9 polymorphism rs11984041 was associated with the LVD stroke subtype in the Vienna Study and the German Study. These results replicated the ISGC/WTCCC2 findings.
- © 2012 by American Heart Association, Inc.