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Non-Caucasian Stroke Genetics

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Stroke Genetics

Abstract

Stroke is the fourth leading cause of death in the United States, but remains the leading cause of death worldwide. Racial and ethnic differences in stroke incidence and subtype may relate to cultural, environmental or genetic variation. Multiple large databases have identified differences in stroke incidence, age of occurrence and outcomes after stroke by race. Here we review the major epidemiologic differences in stroke by race including incidence, presentation age, mortality and differences by subtype are reviewed as a foundation for the subsequent sections.

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References

  1. Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8:355–69.

    Article  PubMed  Google Scholar 

  2. Sacco RL, Boden_Albala B, Gan R, et al. Stroke incidence among white, black, and Hispanic residents of an urban community: the Northern Manhattan Stroke Study. Am J Epidemiol 1998;147:259–268.

    Google Scholar 

  3. Kittner SJ, Cole JW, Hebel JR, et al. Black-White differences in stroke risk: the Baltimore-Washington cooperative young stroke study. Stroke. 2003;34:288–9.

    Google Scholar 

  4. Kissela B, Schneider A, Kleindorfer D, et al. Stroke in a biracial population: the excess burden of stroke among blacks. Stroke. 2004;35:426–31.

    Article  PubMed  Google Scholar 

  5. Howard VJ, Kleindorfer DO, Judd SE, et al. Disparities in stroke incidence contributing to disparities in stroke mortality. Ann Neurol. 2011;69:619–27.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Giles WH, Kittner SJ, Hebel JR, Losonczy KG, Sherwin RW. Determinants of black-white differences in the risk of cerebral infarction. The national health and nutrition examination survey epidemiologic follow-up study. Arch Intern Med. 1995;155:1319–24.

    Article  CAS  PubMed  Google Scholar 

  7. Wright JD, Hughes JP, Ostchega Y, Yoon SS, Nwankwo T. Mean systolic and diastolic blood pressure in adults aged 18 and over in the United States, 2001–2008. Natl Health Stat Rep. 2011;35:1–22.

    Google Scholar 

  8. Feigin V, Carter K, Hackett M, et al. Ethnic disparities in incidence of stroke subtypes: Auckland regional community stroke study, 2002–2003. Lancet Neurol. 2006;5:130–9.

    Article  PubMed  Google Scholar 

  9. Gupta V, Nanda NC, Yesilbursa D, Huang WY, Li Q, Gomez CR. Racial differences in thoracic aorta atherosclerosis among ischemic stroke patients. Stroke. 2003;34:408–12.

    Article  PubMed  Google Scholar 

  10. Carty CL, Keene KL, Cheng YC, et al. Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African Americans. Stroke. 2015;46:2063–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chasman DI, Schurks M, Anttila V, et al. Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat Genet. 2011;43:695–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Harriott AM, Heckman MG, Rayaprolu S, et al. Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk. Eur J Neurol. 2015;22:1235–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang Y, Tong Y, Zhang Y, et al. Two novel susceptibility SNPs for ischemic stroke using exome sequencing in Chinese Han population. Mol Neurobiol. 2014;49:852–62.

    Article  CAS  PubMed  Google Scholar 

  14. Kubo M, Hata J, Ninomiya T, et al. A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat Genet. 2007;39:212–7.

    Article  CAS  PubMed  Google Scholar 

  15. Serizawa M, Nabika T, Ochiai Y, et al. Association between PRKCH gene polymorphisms and subcortical silent brain infarction. Atherosclerosis. 2008;199:340–5.

    Article  CAS  PubMed  Google Scholar 

  16. Cheng H, Wang F, Ding X, Ding H, Song X. Association of PRKCH gene with lacunar infarction in a local Chinese Han population. Neurosci Lett. 2009;464:146–9.

    Article  CAS  PubMed  Google Scholar 

  17. Yamada Y, Fuku N, Tanaka M, et al. Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study. Atherosclerosis. 2009;207:144–9.

    Article  CAS  PubMed  Google Scholar 

  18. Verhaaren BF, Debette S, Bis JC, et al. Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI. Circ Cardiovasc Genet. 2015;8:398–409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ariyaratnam R, Casas JP, Whittaker J, Smeeth L, Hingorani AD, Sharma P. Genetics of ischaemic stroke among persons of non-European descent: a meta-analysis of eight genes involving approximately 32,500 individuals. PLoS Med. 2007;4:e131.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 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;11:951–62.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sacco RL, Blanton SH, Slifer S, et al. Heritability and linkage analysis for carotid intima-media thickness: the family study of stroke risk and carotid atherosclerosis. Stroke. 2009;40:2307–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Havel R, Yamada N, Shames D. Role of apolipoprotein E in lipoprotein metabolism. Am Heart J. 1987;113:470–4.

    Article  CAS  PubMed  Google Scholar 

  23. Lin HF, Lai CL, Tai CT, Lin RT, Liu CK. Apolipoprotein E polymorphism in ischemic cerebrovascular diseases and vascular dementia patients in Taiwan. Neuroepidemiology. 2004;23:129–34.

    Article  PubMed  Google Scholar 

  24. Kim YJ, Lee SM, Cho HJ, et al. Plasma levels of apolipoprotein E and risk of intracranial artery stenosis in acute ischemic stroke patients. Ann Nutr Metab. 2013;62:26–31.

    Article  CAS  PubMed  Google Scholar 

  25. Sturgeon JD, Folsom AR, Bray MS, Boerwinkle E, Ballantyne CM. Atherosclerosis risk in communities study I. Apolipoprotein E genotype and incident ischemic stroke: the atherosclerosis risk in communities study. Stroke. 2005;36:2484–6.

    Article  CAS  PubMed  Google Scholar 

  26. Tang MX, Stern Y, Marder K, et al. The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA. 1998;279:751–5.

    Article  CAS  PubMed  Google Scholar 

  27. Chen C, Hu Z. ApoE polymorphisms and the risk of different subtypes of stroke in the chinese population: a comprehensive meta-analysis. Cerebrovasc Dis. 2016;41:119–38.

    Article  CAS  PubMed  Google Scholar 

  28. Duprez DA. Role of the renin-angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review. J Hypertens. 2006;24:983–91.

    Article  CAS  PubMed  Google Scholar 

  29. Munshi A, Kaul S. Stroke genetics—focus on PDE4D gene. Int J Stroke. 2008;3:188–92.

    Article  PubMed  Google Scholar 

  30. Luo Y, Chen Y, Zhang Y, Gao Y. The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with acute mountain sickness susceptibility: a meta-analysis. High Alt Med Biol. 2012;13:252–7.

    Article  CAS  PubMed  Google Scholar 

  31. Takami S, Imai Y, Katsuya T, et al. Gene polymorphism of the renin-angiotensin system associates with risk for lacunar infarction. The Ohasama study. Am J Hypertens. 2000;13:121–7.

    Article  CAS  PubMed  Google Scholar 

  32. Wang B, Guo Q, Peng Y, Lu J, Singh B, Hua B. Association of AGT M235T and ACE I/D polymorphisms with the risk of ischemic stroke: meta-analysis in Han Chinese population. J Neurol Sci. 2012;320:79–84.

    Article  CAS  PubMed  Google Scholar 

  33. Nakase T, Mizuno T, Harada S, et al. Angiotensinogen gene polymorphism as a risk factor for ischemic stroke. J Clin Neurosci. 2007;14:943–7.

    Article  CAS  PubMed  Google Scholar 

  34. Sethi AA, Tybjaerg-Hansen A, Gronholdt ML, Steffensen R, Schnohr P, Nordestgaard BG. Angiotensinogen mutations and risk for ischemic heart disease, myocardial infarction, and ischemic cerebrovascular disease. Six case-control studies from the Copenhagen city heart study. Ann Intern Med. 2001;134:941–54.

    Article  CAS  PubMed  Google Scholar 

  35. Liang B, Qin L, Wei H, et al. AGT M235T polymorphisms and ischemic stroke risk: a meta-analysis. J Neurol Sci. 2013;331:118–25.

    Article  CAS  PubMed  Google Scholar 

  36. Gretarsdottir S, Thorleifsson G, Reynisdottir ST, et al. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet. 2003;35:131–8.

    Article  CAS  PubMed  Google Scholar 

  37. Nakayama T, Asai S, Sato N, Soma M. Genotype and haplotype association study of the STRK1 region on 5q12 among Japanese: a case-control study. Stroke. 2006;37:69–76.

    Article  CAS  PubMed  Google Scholar 

  38. Caughey MC, Loehr LR, Key NS, et al. Sickle cell trait and incident ischemic stroke in the atherosclerosis risk in communities study. Stroke. 2014;45:2863–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hara K, Shiga A, Fukutake T, et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N Engl J Med. 2009;360:1729–39.

    Article  CAS  PubMed  Google Scholar 

  40. Mendioroz M, Fernandez-Cadenas I, Del Rio-Espinola A, et al. A missense HTRA1 mutation expands CARASIL syndrome to the Caucasian population. Neurology. 2010;75:2033–5.

    Article  CAS  PubMed  Google Scholar 

  41. Fukamizu A, Takahashi S, Seo MS, et al. Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter. J Biol Chem. 1990;265:7576–82.

    CAS  PubMed  Google Scholar 

  42. Kubo M. Genetic risk factors of ischemic stroke identified by a genome-wide association study. Brain Nerve. 2008;60:1339–46.

    CAS  PubMed  Google Scholar 

  43. Broderick JP, Brott T, Tomsick T, Huster G, Miller R. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med. 1992;326:733–6.

    Article  CAS  PubMed  Google Scholar 

  44. Rincon F, Mayer SA. The epidemiology of intracerebral hemorrhage in the United States from 1979 to 2008. Neurocrit Care. 2013;19:95–102.

    Article  PubMed  Google Scholar 

  45. Woo D, Sauerbeck LR, Kissela BM, et al. Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study. Stroke. 2002;33:1190–5.

    Article  PubMed  Google Scholar 

  46. Devan WJ, Falcone GJ, Anderson CD, et al. Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage. Stroke. 2013;44:1578–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Biffi A, Sonni A, Anderson CD, et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol. 2010;68:934–43.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Raffeld MR, Biffi A, Battey TW, et al. APOE epsilon4 and lipid levels affect risk of recurrent nonlobar intracerebral hemorrhage. Neurology. 2015;85:349–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Woo D, Falcone GJ, Devan WJ, et al. Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage. Am J Hum Genet. 2014;94:511–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Traylor M, Zhang CR, Adib-Samii P, et al. Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke. Neurology. 2016;86:146–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tzourio C, Arima H, Harrap S, et al. APOE genotype, ethnicity, and the risk of cerebral hemorrhage. Neurology. 2008;70:1322–8.

    Article  CAS  PubMed  Google Scholar 

  52. Woo D, Kaushal R, Chakraborty R, et al. Association of apolipoprotein E4 and haplotypes of the apolipoprotein E gene with lobar intracerebral hemorrhage. Stroke. 2005;36:1874–9.

    Article  CAS  PubMed  Google Scholar 

  53. Yamada M, Itoh Y, Suematsu N, Matsushita M, Otomo E. Lack of an association between apolipoprotein E epsilon 4 and cerebral amyloid angiopathy in elderly Japanese. Ann Neurol. 1996;39:683–4.

    Article  CAS  PubMed  Google Scholar 

  54. Johnston SC, Selvin S, Gress DR. The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology. 1998;50:1413–8.

    Article  CAS  PubMed  Google Scholar 

  55. Ruigrok YM, Wijmenga C, Rinkel GJ, et al. Genomewide linkage in a large Dutch family with intracranial aneurysms: replication of 2 loci for intracranial aneurysms to chromosome 1p36.11-p36.13 and Xp22.2-p22.32. Stroke. 2008;39:1096–102.

    Article  CAS  PubMed  Google Scholar 

  56. Kissela BM, Sauerbeck L, Woo D, et al. Subarachnoid hemorrhage: a preventable disease with a heritable component. Stroke. 2002;33:1321–6.

    Article  PubMed  Google Scholar 

  57. Woo D, Broderick J. Genetics of intracranial aneurysm. J Stroke Cerebrovasc Dis. 2002;11:230–40.

    Article  PubMed  Google Scholar 

  58. Bromberg JE, Rinkel GJ, Algra A, et al. Subarachnoid haemorrhage in first and second degree relatives of patients with subarachnoid haemorrhage. BMJ. 1995;311:288–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zacharia BE, Hickman ZL, Grobelny BT, et al. Epidemiology of aneurysmal subarachnoid hemorrhage. Neurosurg Clin N Am. 2010;21:221–33.

    Article  PubMed  Google Scholar 

  60. Klatsky AL, Armstrong MA, Friedman GD. Racial differences in cerebrovascular disease hospitalizations. Stroke. 1991;22:299–304.

    Article  CAS  PubMed  Google Scholar 

  61. Ohkuma H, Fujita S, Suzuki S. Incidence of aneurysmal subarachnoid hemorrhage in Shimokita, Japan, from 1989 to 1998. Stroke. 2002;33:195–9.

    Article  PubMed  Google Scholar 

  62. Ayala C, Greenlund KJ, Croft JB, et al. Racial/ethnic disparities in mortality by stroke subtype in the United States, 1995-1998. Am J Epidemiol. 2001;154:1057–63.

    Article  CAS  PubMed  Google Scholar 

  63. Eden SV, Meurer WJ, Sanchez BN, et al. Gender and ethnic differences in subarachnoid hemorrhage. Neurology. 2008;71:731–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Krex D, Konig IR, Ziegler A, Schackert HK, Schackert G. Extended single nucleotide polymorphism and haplotype analysis of the elastin gene in Caucasians with intracranial aneurysms provides evidence for racially/ethnically based differences. Cerebrovasc Dis. 2004;18:104–10.

    Article  CAS  PubMed  Google Scholar 

  65. Takenaka K, Sakai H, Yamakawa H, et al. Polymorphism of the endoglin gene in patients with intracranial saccular aneurysms. J Neurosurg. 1999;90:935–8.

    Article  CAS  PubMed  Google Scholar 

  66. Joo SP, Lee JK, Kim TS, et al. A polymorphic variant of the endoglin gene is associated with increased risk for intracranial aneurysms in a Korean population. Surg Neurol. 2008;70:39–44.

    Article  PubMed  Google Scholar 

  67. Onda H, Kasuya H, Yoneyama T, Hori T, Nakajima T, Inoue I. Endoglin is not a major susceptibility gene for intracranial aneurysm among Japanese. Stroke. 2003;34:1640–4.

    Article  CAS  PubMed  Google Scholar 

  68. Peters DG, Kassam AB, Chang YF. A DNA sequence polymorphism in the endoglin gene is not associated with intracranial aneurysm or aneurysmal subarachnoid hemorrhage. Cerebrovasc Dis. 2005;20:96–100.

    Article  CAS  PubMed  Google Scholar 

  69. Pera J, Slowik A, Dziedzic T, et al. Endoglin gene insertion polymorphism not associated with aneurysmal subarachnoid hemorrhage. J Neurosurg. 2005;102:879–81.

    Article  CAS  PubMed  Google Scholar 

  70. Onda H, Kasuya H, Yoneyama T, et al. Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11. Am J Hum Genet. 2001;69:804–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Akagawa H, Narita A, Yamada H, et al. Systematic screening of lysyl oxidase-like (LOXL) family genes demonstrates that LOXL2 is a susceptibility gene to intracranial aneurysms. Hum Genet. 2007;121:377–87.

    Article  CAS  PubMed  Google Scholar 

  72. Sathyan S, Koshy L, Sarada Lekshmi KR, et al. Lack of association of lysyl oxidase (LOX) gene polymorphisms with intracranial aneurysm in a south Indian population. Mol Biol Rep. 2013;40:5869–74.

    Article  CAS  PubMed  Google Scholar 

  73. Low SK, Takahashi A, Cha PC, et al. Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA. Hum Mol Genet. 2012;21:2102–10.

    Article  CAS  PubMed  Google Scholar 

  74. Suo M, Lin Y, Yu H, et al. Association of Kallikrein gene polymorphisms with sporadic intracranial aneurysms in the Chinese population. J Neurosurg. 2014;120:1397–401.

    Article  CAS  PubMed  Google Scholar 

  75. Akagawa H, Tajima A, Sakamoto Y, et al. A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms. Hum Mol Genet. 2006;15:1722–34.

    Article  CAS  PubMed  Google Scholar 

  76. Yoshida T et al. Association of genetic variants with hemorrhagic stroke in Japanese individuals. Int J Mol Med. 2010;25(4):649–56.

    Google Scholar 

  77. Chen C and Hu Z. ApoE polymorphisms and the risk of different subtypes of stroke in the Chinese population: A comprehensive meta-analysis. Cerebrovasc Dis. 2016;41(3-4);119–38.

    Google Scholar 

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Correspondence to Daniel Woo M.D., M.S. .

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Demel, S.L., Woo, D. (2017). Non-Caucasian Stroke Genetics. In: Sharma, P., Meschia, J. (eds) Stroke Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-56210-0_15

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