原创力文档causal relationship of susceptibility genes to ischemic stroke comparison to ischemic heart disease and biochemical determinants因果关系的易感基因缺血性中风与缺血性心脏病和生化因素.pdfVIP
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causal relationship of susceptibility genes to ischemic stroke comparison to ischemic heart disease and biochemical determinants因果关系的易感基因缺血性中风与缺血性心脏病和生化因素
Causal Relationship of Susceptibility Genes to Ischemic
Stroke: Comparison to Ischemic Heart Disease and
Biochemical Determinants
1 1 2 2 1
Paul Bentley *, George Peck , Liam Smeeth , John Whittaker , Pankaj Sharma
1 Imperial College Cerebrovascular Research Unit, Clinical Neurosciences, Charing Cross Hospital, Imperial College London, London, United Kingdom, 2 Department of
Epidemiology and Population Health, London School of Hygiene Tropical Medicine, London, United Kingdom
Abstract
Interrelationships between genetic and biochemical factors underlying ischemic stroke and ischemic heart disease are poorly
understood. We: 1) undertook the most comprehensive meta-analysis of genetic polymorphisms in ischemic stroke to date; 2)
compared genetic determinants of ischemic stroke with those of ischemic heart disease, and 3) compared effect sizes of gene-
stroke associations with those predicted from independent biochemical data using a mendelian randomization strategy.
Electronic databases were searched up to January 2009. We identified: 1) 187 ischemic stroke studies (37,481 cases; 95,322
controls) interrogating 43 polymorphisms in 29 genes; 2) 13 meta-analyses testing equivalent polymorphisms in ischemic
heart disease; and 3) for the top five gene-stroke associations, 146 studies (65,703 subjects) describing equivalent gene-
biochemical relationships, and 28 studies (46,928 subjects) describing biochemical-stroke relationships. Meta-analyses
demonstrated positive associations with ischemic stroke for factor V Leiden Gln506, ACE I/D, MTHFR C677T, prothrombin
G20210A, PAI-1 5G allele and glycoprotein IIIa Leu33Pro polymorphisms (ORs: 1.11 – 1.60). Most genetic associations show
congruent levels of risk comparing isch
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