Abstract
Genome-wide association studies have demonstrated various polymorphisms of histone deacetylase 9 (HDAC9) gene was strong risk locus for large-vessel stroke, but the results were controversial. This study aims to replicate the association between the previous detected SNPs of HDAC9 and the susceptibility of ischemic stroke. The study population consisted of 262 consecutive patients diagnosed with ischemic stroke and 300 age and gender matched unrelated controls between October 2012 and October 2014. Rs11984041, rs2389995, and rs2240419 of HDAC9 were genotyped and compared between the cases and controls. The SNP rs11984041 of HDAC9 was found nonpolymorphic in the population involved. The G allele of rs2389995 was found significantly associated with decreased risk of ischemic stroke, no matter with the codominant (AG v.s AA, 0.53 (0.36–0.77), P < 0.001; GG v.s AA, 0.63 (0.27–1.43), P < 0.001), dominant (AG + GG v.s AA, 0.54 (0.38–0.78), P < 0.001), or the recessive model (GG vs AA + AG, 0.75 (0.33–1.71), P < 0.001). On the other hand, The T allele of rs2240419 was found significantly associated with increased risk of ischemic stroke, no matter with the codominant (CT v.s CC, 1.75 (1.22–2.51), P < 0.001; TT v.s CC, 2.67 (1.55–4.61), P < 0.001), dominant (CT + TT v.s CC, 1.93 (1.38–2.71), P < 0.001), or the recessive model (TT vs CC + CT, 2.07 (1.23–3.47), P < 0.001). No linkage disequilibrium was found between rs2389995 and rs2240419 of HDAC9. In conclusion, the present study demonstrated the SNP rs11984041 of HDAC9 was nonpolymorphic in Chinese Han population. The minor G allele of rs2389995 significantly decreased and the minor T allele of rs2240419 significantly increased the risk of ischemic stroke.
Similar content being viewed by others
References
Lozano R, Naghavi M, Foreman K, et al. (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet 380(9859):2095–2128. doi:10.1016/S0140-6736(12)61728-0
Ross R (1999) Atherosclerosis–an inflammatory disease. N Engl J Med 340(2):115–126. doi:10.1056/NEJM199901143400207
Weber C, Noels H (2011) Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 17(11):1410–1422. doi:10.1038/nm.2538
International Stroke Genetics C, Wellcome Trust Case Control C, Bellenguez C et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet. 2012;44(3):328–33. doi:10.1038/ng.1081
Consortium CAD, Deloukas P, Kanoni S, et al. (2013) Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 45(1):25–33. doi:10.1038/ng.2480
Markus HS, Makela KM, Bevan S et al. Evidence HDAC9 genetic variant associated with ischemic stroke increases risk via promoting carotid atherosclerosis. Stroke; J. Cereb. Circ. 2013;44(5):1220–5. doi:10.1161/STROKEAHA.111.000217
Han Y, Sun W, Wang L et al. HDAC9 gene is associated with stroke risk in a Chinese population. Exp. Biol. Med.. 2013;238(7):842–7. doi:10.1177/1535370213494650.
Jia Q, Liu L, Wang Y (2011) Risk factors and prevention of stroke in the Chinese population. J. Stroke Cereb. Dis. : Off. J. Natl. Stroke Assoc 20(5):395–400. doi:10.1016/j.jstrokecerebrovasdis.2010.02.008
Kim YD, Cha MJ, Kim J, et al. (2013) Long-term mortality in patients with coexisting potential causes of ischemic stroke. Int. J. Stroke : Off. J. Int. Stroke Soc. doi:10.1111/ijs.12013
Dichgans M, Malik R, Konig IR, et al. (2014) Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. Stroke; J. Cereb. Circ 45(1):24–36. doi:10.1161/STROKEAHA.113.002707
Traylor M, Farrall M, Holliday EG et al. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. Lancet Neurol. 2012;11(11):951–962. doi:10.1016/S1474-4422(12)70234-X.
Lee JD, Lee TH, Huang YC, et al. (2011) ALOX5AP genetic variants and risk of atherothrombotic stroke in the Taiwanese population. J. Clin. Neurosci.: Off. J. Neurosurg. Soc. Aust 18(12):1634–1638. doi:10.1016/j.jocn.2011.03.035
Groenen PM, Vanderlinden G, Devriendt K, Fryns JP, Van de Ven WJ (1998) Rearrangement of the human CDC5L gene by a t(6;19)(p21;q13.1) in a patient with multicystic renal dysplasia. Genomics 49(2):218–229. doi:10.1006/geno.1998.5254
Markus HS (2013) WellcomeTrust genome-wide association study of ischemic stroke. Stroke; J. Cereb. Circ 44(6 Suppl 1):S20–S22. doi:10.1161/STROKEAHA.112.680652
Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10(1):32–42. doi:10.1038/nrg2485
Chang S, McKinsey TA, Zhang CL, et al. (2004) Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development. Mol Cell Biol 24(19):8467–8476. doi:10.1128/MCB.24.19.8467-8476.2004
Langley B, Brochier C, Rivieccio MA (2009) Targeting histone deacetylases as a multifaceted approach to treat the diverse outcomes of stroke. Stroke; J. Cereb. Circ. 40(8):2899–2905. doi:10.1161/STROKEAHA.108.540229
Holliday EG, Maguire JM, Evans TJ, et al. (2012) Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nat Genet 44(10):1147–1151. doi:10.1038/ng.2397
Cao Q, Rong S, Repa JJ et al. Histone deacetylase 9 represses cholesterol efflux and alternatively activated macrophages in atherosclerosis development. Arterioscler. Thromb. Vasc. Biol.. 2014;34(9):1871–9. doi:10.1161/ATVBAHA.114.303393
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
qingxu, G., Yan, Z., Jiannan, X. et al. Association Between the Gene Polymorphisms of HDAC9 and the Risk of Atherosclerosis and Ischemic Stroke. Pathol. Oncol. Res. 22, 103–107 (2016). https://doi.org/10.1007/s12253-015-9978-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12253-015-9978-8