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Gretarsdottir S Thorleifsson G Reynisdottir ST Manolescu A Jonsdottir S Jonsdottir T Gudmundsdottir T Bjarnadottir SM Einarsson OB Gudjonsdottir HM Hawkins M Gudmundsson G Gudmundsdottir H Andrason H Gudmundsdottir AS Sigurdardottir M Chou TT Nahmias J Goss S Sveinbjörnsdottir S Valdimarsson EM Jakobsson F Agnarsson U Gudnason V Thorgeirsson G Fingerle J Gurney M Gudbjartsson D Frigge ML Kong A Stefansson K Gulcher JR 《Nature genetics》2003,35(2):131-138
We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke. 相似文献
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Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes 总被引:1,自引:0,他引:1
Grant SF Thorleifsson G Reynisdottir I Benediktsson R Manolescu A Sainz J Helgason A Stefansson H Emilsson V Helgadottir A Styrkarsdottir U Magnusson KP Walters GB Palsdottir E Jonsdottir T Gudmundsdottir T Gylfason A Saemundsdottir J Wilensky RL Reilly MP Rader DJ Bagger Y Christiansen C Gudnason V Sigurdsson G Thorsteinsdottir U Gulcher JR Kong A Stefansson K 《Nature genetics》2006,38(3):320-323
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The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke 总被引:29,自引:0,他引:29
Helgadottir A Manolescu A Thorleifsson G Gretarsdottir S Jonsdottir H Thorsteinsdottir U Samani NJ Gudmundsson G Grant SF Thorgeirsson G Sveinbjornsdottir S Valdimarsson EM Matthiasson SE Johannsson H Gudmundsdottir O Gurney ME Sainz J Thorhallsdottir M Andresdottir M Frigge ML Topol EJ Kong A Gudnason V Hakonarson H Gulcher JR Stefansson K 《Nature genetics》2004,36(3):233-239
We mapped a gene predisposing to myocardial infarction to a locus on chromosome 13q12-13. A four-marker single-nucleotide polymorphism (SNP) haplotype in this locus spanning the gene ALOX5AP encoding 5-lipoxygenase activating protein (FLAP) is associated with a two times greater risk of myocardial infarction in Iceland. This haplotype also confers almost two times greater risk of stroke. Another ALOX5AP haplotype is associated with myocardial infarction in individuals from the UK. Stimulated neutrophils from individuals with myocardial infarction produce more leukotriene B4, a key product in the 5-lipoxygenase pathway, than do neutrophils from controls, and this difference is largely attributed to cells from males who carry the at-risk haplotype. We conclude that variants of ALOX5AP are involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall. 相似文献
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