Common Mitochondrial Sequence Variants in Ischemic Stroke

被引：32

作者：

Anderson, Christopher D. ^{[1
,2
,3
]}

Biffi, Alessandro ^{[1
,2
,3
]}

Rahman, Rosanna ^{[1
,2
,3
]}

Ross, Owen A. ^{[4
]}

Jagiella, Jeremiasz M. ^{[5
]}

Kissela, Brett ^{[6
]}

Cole, John W. ^{[7
]}

Cortellini, Lynelle ^{[1
,2
,3
]}

Rost, Natalia S. ^{[1
,2
,3
]}

Cheng, Yu-Ching ^{[7
]}

Greenberg, Steven M. ^{[2
]}

de Bakker, Paul I. W. ^{[3
,8
]}

Brown, Robert D., Jr. ^{[9
]}

Brott, Thomas G. ^{[4
]}

Mitchell, Braxton D. ^{[7
]}

Broderick, Joseph P. ^{[6
]}

Worrall, Bradford B. ^{[10
]}

Furie, Karen L. ^{[1
,2
]}

Kittner, Steven J. ^{[7
]}

Woo, Daniel ^{[6
]}

Slowik, Agnieszka ^{[5
]}

Meschia, James F. ^{[4
]}

Saxena, Richa ^{[1
,3
]}

Rosand, Jonathan ^{[1
,2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[3] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[4] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[5] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland

[6] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA

[7] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA

[8] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA

[9] Mayo Clin, Dept Neurol, Rochester, MN USA

[10] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA

来源：

ANNALS OF NEUROLOGY | 2011年 / 69卷 / 03期

关键词：

WHITE-MATTER LESIONS; ASSOCIATION; POWER; EPIDEMIOLOGY; DISEASE; RISK;

D O I：

10.1002/ana.22108

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: Rare mitochondrial mutations cause neurologic disease, including ischemic stroke and MRI white matter changes. We investigated whether common mitochondrial genetic variants influence risk of sporadic ischemic stroke and, in patients with stroke, the volume of white matter hyperintensity (WMHV). Methods: In this multicenter, mitochondrial genome-wide association study (GWAS), 2284 ischemic stroke cases and 1728 controls from the International Stroke Genetics Consortium were genotyped for 64 mitochondrial single nucleotide polymorphisms (SNPs). Imputation resulted in 144 SNPs, which were tested in each cohort and in meta-analysis for ischemic stroke association. A genetic score of all mitochondrial variants was also tested in association with ischemic stroke. Results: No individual SNP reached adjusted significance in meta-analysis. A genetic score comprised of the summation of contributions from individual variants across the mitochondrial genome showed association with ischemic stroke in meta-analysis (odds ratio [OR] 1.13, p < 0.0001) with minimal heterogeneity (I-2 = 0.00). This ischemic stroke score was robust to permutation, and was also associated with WMHV in 792 nested case individuals with ischemic stroke (p = 0.037). Interpretation: In this mitochondrial GWAS of ischemic stroke, a genetic score comprised of the sum of all common variants in the mitochondrial genome showed association with ischemic stroke. In an independent analysis of a related trait, this same score correlated with WMHV in stroke cases. Despite this aggregate association, no individual variant reached significance. Substantially larger studies will be required to identify precise sequence variants influencing cerebrovascular disease. ANN NEUROL 2011;69:471-480

引用

页码：471 / 480

页数：10

共 33 条

[1] CLASSIFICATION OF SUBTYPE OF ACUTE ISCHEMIC STROKE - DEFINITIONS FOR USE IN A MULTICENTER CLINICAL-TRIAL [J].

ADAMS, HP ;

BENDIXEN, BH ;

KAPPELLE, LJ ;

BILLER, J ;

LOVE, BB ;

GORDON, DL ;

MARSH, EE ;

KASE, CS ;

WOLF, PA ;

BABIKIAN, VL ;

LICATAGEHR, EE ;

ALLEN, N ;

BRASS, LM ;

FAYAD, PB ;

PAVALKIS, FJ ;

WEINBERGER, JM ;

TUHRIM, S ;

RUDOLPH, SH ;

HOROWITZ, DR ;

BITTON, A ;

MOHR, JP ;

SACCO, RL ;

CLAVIJO, M ;

ROSENBAUM, DM ;

SPARR, SA ;

KATZ, P ;

KLONOWSKI, E ;

CULEBRAS, A ;

CAREY, G ;

MARTIR, NI ;

FICARRA, C ;

HOGAN, EL ;

CARTER, T ;

GURECKI, P ;

MUNTZ, BK ;

RAMIREZLASSEPAS, M ;

TULLOCH, JW ;

QUINONES, MR ;

MENDEZ, M ;

ZHANG, SM ;

ALA, T ;

JOHNSTON, KC ;

ANDERSON, DC ;

TARREL, RM ;

NANCE, MA ;

BUDLIE, SR ;

DIERICH, M ;

HELGASON, CM ;

HIER, DB ;

SHAPIRO, RA .

STROKE, 1993, 24 (01) :35-41

[2] Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke [J].

Arsava, E. M. ;

Rahman, R. ;

Rosand, J. ;

Lu, J. ;

Smith, E. E. ;

Rost, N. S. ;

Singhal, A. B. ;

Lev, M. H. ;

Furie, K. L. ;

Koroshetz, W. J. ;

Sorensen, A. G. ;

Ay, H. .

NEUROLOGY, 2009, 72 (16) :1403-1410

[3] Principal-Component Analysis for Assessment of Population Stratification in Mitochondrial Medical Genetics [J].

Biffi, Alessandro ;

Anderson, Christopher D. ;

Nalls, Michael A. ;

Rahman, Rosanna ;

Sonni, Akshata ;

Cortellini, Lynelle ;

Rost, Natalia S. ;

Matarin, Mar ;

Hernandez, Dena G. ;

Plourde, Anna ;

de Bakker, Paul I. W. ;

Ross, Owen A. ;

Greenberg, Steven M. ;

Furie, Karen L. ;

Meschia, James F. ;

Singleton, Andrew B. ;

Saxena, Richa ;

Rosand, Jonathan .

AMERICAN JOURNAL OF HUMAN GENETICS, 2010, 86 (06) :904-917

[4]

BRODERICK JP, 1996, NEUROEPIDEMIOLOGY, V15, P19

[5] Progression of white matter lesions and hemorrhages in cerebral amyloid angiopathy [J].

Chen, Y. W. ;

Gurol, M. E. ;

Rosand, J. ;

Viswanathan, A. ;

Rakich, S. M. ;

Groover, T. R. ;

Greenberg, S. M. ;

Smith, E. E. .

NEUROLOGY, 2006, 67 (01) :83-87

[6] Mitochondrial DNA haplogroups and risk of transient ischaemic attack and ischaemic stroke: a genetic association study [J].

Chinnery, Patrick F. ;

Elliott, Hannah R. ;

Syed, Anila ;

Rothwell, Peter M. .

LANCET NEUROLOGY, 2010, 9 (05) :498-503

[7] Mitochondrial disorders in the nervous system [J].

DiMauro, Salvatore ;

Schon, Eric A. .

ANNUAL REVIEW OF NEUROSCIENCE, 2008, 31 :91-123

[8] Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century [J].

Feigin, VL ;

Lawes, CMM ;

Bennett, DA ;

Anderson, CS .

LANCET NEUROLOGY, 2003, 2 (01) :43-53

[9] Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke [J].

Flossmann, E ;

Schulz, UGR ;

Rothwell, PM .

STROKE, 2004, 35 (01) :212-227

[10] Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke [J].

Fu, JH ;

Lu, CZ ;

Hong, Z ;

Dong, Q ;

Luo, Y ;

Wong, KS .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2005, 76 (06) :793-796

← 1 2 3 4 →