|
|
Genetics of ischemic and hemorrhagic stroke in
Chinese population |
Wei-Li ZHANG MD, PhD1,Ru-Tai HUI MD, PhD2, |
1.Sino-German Laboratory
for Molecular Medicine, the Key Laboratory for Clinical Cardiovascular
Genetics, Beijing 100037, China; 2.Sino-German Laboratory
for Molecular Medicine, the Key Laboratory for Clinical Cardiovascular
Genetics, Beijing 100037, China;Hypertension Division,
Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical
Sciences, Beijing 100037, China; |
|
|
Abstract Stroke is a major cause of adult death and disability worldwide. Epidemiological and animal studies have provided strong evidence that the pathogenesis of stroke is multi-factorial and induced by a combination of environmental and genetic risk factors, but the identification of individual causative variants remains little known. Genetic influences are likely to be polygenic with small effect sizes, and stroke itself consists of a number of different subtypes which may each have different genetic profiles. In addition, various ethnic populations may have different stroke risk, such as Asian race. The reasons for high risk of stroke among the Chinese, especially hemorrhagic stroke, remain unknown. Most human studies have taken a candidate gene approach using case-control methodology. To be reliably detected, small relative risks require large sample sizes, probably 1000 patients or more. Genome-wide association (GWA) study is an unbiased and comprehensive approach to identify common risk alleles for complex diseases. Recently, a multistage GWA study has identified three loci on chromosomes 2q, 8q and 9p to be associated with intracranial aneurysm in European and Japanese populations. Another GWA finding is the identification of risk variants for cardioembolic stroke on chromosome 4q25 in European populations. In this review, we mainly focus on the results from case-control association studies on genetic factors that play a role in the risk of ischemic and hemorrhagic stroke in Chinese population. The combined effects of multiple susceptibility genes for stroke risk are also summarized.
|
Keywords
genetics
ischemic stroke
hemorrhagic stroke
association study
|
Issue Date: 05 March 2010
|
|
|
Liu M, Wu B, Wang W Z, Lee L M, Zhang S H, Kong L Z. Stroke in China: epidemiology, prevention, and managementstrategies. Lancet Neurol, 2007, 6 (5): 456–464
doi: 10.1016/S1474-4422(07)70004-2
|
|
Reed D M. The paradox of high risk of stroke in populations withlow risk of coronary heart disease. AmJ Epidemiol, 1990, 131(4): 579–588
|
|
Flossmann E, Schulz U G, Rothwell P M. Systematic review of methodsand results of studies of the genetic epidemiology of ischemic stroke. Stroke, 2004, 35(1): 212–227
doi: 10.1161/01.STR.0000107187.84390.AA
|
|
Adams H P Jr, Bendixen B H, Kappelle L J, Biller J, Love B B, Gordon D L. Classification of subtype of acute ischemicstroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment.Stroke, 1993, 24(1): 35–41
|
|
Schulz U G, Flossmann E, Rothwell P M. Heritability of ischemicstroke in relation to age, vascular risk factors, and subtypes ofincident stroke in population-based studies. Stroke, 2004, 35(4): 819–824
doi: 10.1161/01.STR.0000121646.23955.0f
|
|
Jerrard-Dunne P, Cloud G, Hassan A, Markus H S. Evaluating the genetic component of ischemic stroke subtypes: a familyhistory study. Stroke, 2003, 34(6): 1364–1369
doi: 10.1161/01.STR.0000069723.17984.FD
|
|
Qureshi A I, Tuhrim S, Broderick J P, Batjer H H, Hondo H, Hanley D F. Spontaneous intracerebral hemorrhage. N Engl J Med, 2001, 344(19): 1450–1460
doi: 10.1056/NEJM200105103441907
|
|
Healy D G. Case-control studies in the genomic era: a clinician’sguide. Lancet Neurol, 2006, 5(8): 701–707
doi: 10.1016/S1474-4422(06)70524-5
|
|
Li Z, Sun L, Zhang H, Liao Y, Wang D, Zhao B, Zhu Z, Zhao J, Ma A, Han Y, Wang Y, Shi Y, Ye J, Hui R. Elevated plasmahomocysteine was associated with hemorrhagic and ischemic stroke,but methylenetetrahydrofolate reductase gene C677T polymorphism wasa risk factor for thrombotic stroke: a Multicenter Case-Control Studyin China. Stroke, 2003, 34(9): 2085–2090
doi: 10.1161/01.STR.0000086753.00555.0D
|
|
Wald D S, Law M, Morris J K. Homocysteine and cardiovascular disease:evidence on causality from a meta-analysis. BMJ, 2002, 325(7374): 1202
doi: 10.1136/bmj.325.7374.1202
|
|
Kang S S, Zhou J, Wong P W, Kowalisyn J, Strokosch G. Intermediate homocysteinemia:a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet, 1988, 43(4): 414–421
|
|
Morita H, Kurihara H, Tsubaki S, Sugiyama T, Hamada C, Kurihara Y, Shindo T, Oh-Hashi Y, Kitamura K, Yazaki Y. Methylenetetrahydrofolate reductase gene polymorphismand ischemic stroke in Japanese. ArteriosclerThromb Vasc Biol, 1998, 18(9): 1465–1469
|
|
Zhang W, Sun K, Chen J, Liao Y, Qin Q, Ma A, Wang D, Zhu Z, Wang Y, Hui R. High plasma homocysteinelevels contribute to the risk of stroke recurrence and all-cause mortalityin a large prospective stroke population. Clin Sci (Lond), 2010, 118(3): 187–194
doi: 10.1042/CS20090142
|
|
Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X. Efficacyof folic acid supplementation in stroke prevention: a meta-analysis. Lancet, 2007, 369(9576): 1876–1882
doi: 10.1016/S0140-6736(07)60854-X
|
|
Zhao C X, Cui Y H, Fan Q, Wang P H, Hui R, Cianflone K, Wang D W. Small denselow-density lipoproteins and associated risk factors in patients withstroke. Cerebrovasc Dis, 2009, 27(1): 99–104
doi: 10.1159/000175768
|
|
Brazier L, Tiret L, Luc G, Arveiler D, Ruidavets J B, Evans A, Chapman J, Cambien F, Thillet J. Sequence polymorphisms in the apolipoprotein(a) geneand their association with lipoprotein(a) levels and myocardial infarction:the ECTIM Study. Atherosclerosis, 1999, 144(2): 323–333
doi: 10.1016/S0021-9150(98)00333-5
|
|
Peng D Q, Zhao S P, Wang J L. Lipoprotein(a) and apolipoprotein E epsilon4 as independent risk factors for ischemic stroke. J Cardiovasc Risk, 1999, 6(1): 1–6
|
|
Scholz M, Kraft H G, Lingenhel A, Delport R, Vorster E H, Bickeboller H, Utermann G. Geneticcontrol of lipoprotein(a) concentrations is different in Africansand Caucasians. Eur J Hum Genet, 1999, 7(2): 169–178
doi: 10.1038/sj.ejhg.5200290
|
|
Sandholzer C, Hallman D M, Saha N, Sigurdsson G, Lackner C, Csaszar A, Boerwinkle E, Utermann G. Effectsof the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentrationin 7 ethnic groups. Hum Genet, 1991, 86(6): 607–614
doi: 10.1007/BF00201550
|
|
Trommsdorff M, Kochl S, Lingenhel A, Kronenberg F, Delport R, Vermaak H, Lemming L, Klausen I C, Faergeman O, Utermann G. Apentanucleotide repeat polymorphism in the 5' control region of theapolipoprotein(a) gene is associated with lipoprotein(a) plasma concentrationsin Caucasians. J Clin Invest, 1995, 96(1): 150–157
doi: 10.1172/JCI118015
|
|
Sun L, Li Z, Zhang H, Ma A, Liao Y, Wang D, Zhao B, Zhu Z, Zhao J, Zhang Z, Wang W, Hui R. PentanucleotideTTTTA repeat polymorphism of apolipoprotein(a) gene and plasma lipoprotein(a)are associated with ischemic and hemorrhagic stroke in Chinese: amulticenter case-control study in China. Stroke, 2003, 34(7): 1617–1622
doi: 10.1161/01.STR.0000078370.12085.02
|
|
Wang Y, Zhen Y, Shi Y, Chen J, Zhang C, Wang X, Yang X, Zheng Y, Liu Y, Hui R. Vitamin K epoxide reductase:a protein involved in angiogenesis. MolCancer Res, 2005, 3(6): 317–323
doi: 10.1158/1541-7786.MCR-04-0221
|
|
Rieder M J, Reiner A P, Gage B F, Nickerson D A, Eby C S, McLeod H L, Blough D K, Thummel K E, Veenstra D L, Rettie A E. Effect of VKORC1 haplotypes on transcriptional regulation and warfarindose. N Engl J Med, 2005, 352(22): 2285–2293
doi: 10.1056/NEJMoa044503
|
|
Wang Y, Zhang W, Zhang Y, Yang Y, Sun L, Hu S, Chen J, Zhang C, Zheng Y, Zhen Y, Sun K, Fu C, Yang T, Wang J, Sun J, Wu H, Glasgow W C, Hui R. VKORC1 haplotypes are associatedwith arterial vascular diseases (stroke, coronary heart disease, andaortic dissection). Circulation, 2006, 113(12): 1615–1621
doi: 10.1161/CIRCULATIONAHA.105.580167
|
|
Moulton K S. Angiogenesis in atherosclerosis: gathering evidence beyondspeculation. Curr Opin Lipidol, 2006, 17(5): 548–555
doi: 10.1097/01.mol.0000245261.71129.f0
|
|
Celletti F L, Waugh J M, Amabile P G, Brendolan A, Hilfiker P R, Dake M D. Vascular endothelial growth factor enhances atheroscleroticplaque progression. Nat Med, 2001, 7(4): 425–442
doi: 10.1038/86490
|
|
Cleaver O, Melton D A. Endothelial signaling during development. Nat Med, 2003, 9(6): 661–668
doi: 10.1038/nm0603-661
|
|
Zhang W, Sun K, Zhen Y, Wang D, Wang Y, Chen J, Xu J, Hu F B, Hui R. VEGFreceptor-2 variants are associated with susceptibility to stroke andrecurrence. Stroke, 2009, 40(8): 2720–2726
doi: 10.1161/STROKEAHA.109.554394
|
|
Wang Y, Zheng Y, Zhang W, Yu H, Lou K, Zhang Y, Qin Q, Zhao B, Yang Y, Hui R. Polymorphisms of KDR geneare associated with coronary heart disease. J Am Coll Cardiol, 2007, 50(8): 760–767
doi: 10.1016/j.jacc.2007.04.074
|
|
Chen J, Yu H, Song W, Sun K, Song Y, Lou K, Yang T, Zhang Y, Hui R. Angiopoietin-2promoter haplotypes confer an increased risk of stroke in a ChineseHan population. Clin Sci (Lond), 2009, 117(11): 387–395
doi: 10.1042/CS20090035
|
|
Vallance P and Leiper J. Cardiovascularbiology of the asymmetric dimethylarginine: dimethylarginine dimethylaminohydrolasepathway. Arterioscler Thromb Vasc Biol, 2004, 24(6): 1023–1030
doi: 10.1161/01.ATV.0000128897.54893.26
|
|
Bai Y, Chen J, Sun K, Xin Y, Liu J, Hui R. Common genetic variation in DDAH2 is associated withintracerebral haemorrhage in a Chinese population: a multi-centrecase-control study in China. Clin Sci (Lond), 2009, 117(7): 273–279
doi: 10.1042/CS20090005
|
|
|
|
Song Q, Cole J W, O'Connell J R, Stine O C, Gallagher M, Giles W H, Mitchell B D, Wozniak M A, Stern B J, Sorkin J D, McArdle P F, Naj A C, Xu Q, Gibbons G H, Kittner S J. Phosphodiesterase 4D polymorphismsand the risk of cerebral infarction in a biracial population: thestroke prevention in young women study. Hum Mol Genet, 2006, 15(16): 2468–2478
|
|
Xue H, Wang H, Song X, Li W, Sun K, Zhang W, Wang X, Wang Y, Hui R. Phosphodiesterase4D gene polymorphism is associated with ischaemic and haemorrhagicstroke. Clin Sci (Lond), 2009, 116(4): 335–340
|
|
|
|
Zhang W L, Yang X M, Shi J, Sun K, Hui R T. Polymorphism of SG13S114T/Ain the ALOX5AP gene and the risk for stroke in a large Chinese cohort. Yi Chuan Xue Bao, 2006, 33(8): 678–684 (in Chinese)
|
|
Wang Q, Ding H, Tang J R, Zhang L, Xu YJ, Yan JT, Wang W, Hui R T, Wang CY, Wang D W. C-reactive protein polymorphismsand genetic susceptibility to ischemic stroke and hemorrhagic strokein the Chinese Han population. Acta PharmacolSin, 2009, 30(3): 291–298
|
|
Song W, Chen J, Sun K, Yu H, Hui R. No association of PLIN polymorphismswith hemorrhagic and ischemic stroke. Stroke, 2008, 39(2): 470–472
|
|
Zhang L, Ding H, Yan J, Hui R, Wang W, Kissling G E, Zeldin D C, Wang D W. Genetic variation in cytochromeP450 2J2 and soluble epoxide hydrolase and risk of ischemic strokein a Chinese population. PharmacogenetGenomics, 2008, 18(1): 45–51
|
|
Zhang L, Zhang H, Sun K, Song Y, Hui R, Huang X. The 825C/T polymorphism of G-protein beta3 subunit geneand risk of ischaemic stroke. J Hum Hypertens, 2005, 19(9): 709–714
|
|
Ritchie M D, Hahn L W, Roodi N, Bailey L R, Dupont W D, Parl F F, Moore J H. Multifactor-dimensionalityreduction reveals high order interactions among estrogen-metabolismgenes in sporadic breast cancer. Am J HumGenet, 2001, 69(1): 138–147
|
|
Shen C D, Zhang W L, Sun K, Wang Y B, Zhen Y S, Hui R T. Interaction of genetic risk factors confers higher riskfor thrombotic stroke in male Chinese: a multicenter case-controlstudy. Ann Hum Genet, 2007, 71(Pt 5): 620–629
|
|
Liu J, Sun K, Bai Y, Zhang W, Wang X, Wang Y, Wang H, Chen J, Song X, Xin Y, Liu Z, Hui R. Associationof three-gene interaction among MTHFR, ALOX5AP and NOTCH3 with thromboticstroke: a multicenter case-control study. Hum Genet, 2009, 125(5,6): 649–656
|
|
|
|
|
|
Kim I, Saunders T L, Morrison S J. Sox17 dependence distinguishesthe transcriptional regulation of fetal from adult hematopoietic stemcells. Cell, 2007, 130(3): 470–483
doi: 10.1016/j.cell.2007.06.011
|
|
Janzen V, Forkert R, Fleming H E, Saito Y, Waring M T, Dombkowski D M, Cheng T, DePinho R A, Sharpless N E, Scadden D T. Stem-cell ageing modified by the cyclin-dependent kinaseinhibitor p16INK4a. Nature, 2006, 443(7110): 421–426
|
|
|
|
Pollex R L, Hegele R A. Copy number variation in the human genome and its implications forcardiovascular disease. Circulation, 2007, 115(24): 3130–3138
doi: 10.1161/CIRCULATIONAHA.106.677591
|
|
Rieder M J, Reiner A P, Gage B F. Effect of VKORC1 haplotypeson transcriptional regulation and warfarin dose. N Engl J Med, 2005, 352(22): 2285–2293
doi: 10.1056/NEJMoa044503
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|