The gene encoding phosphodiesterase 4D confers risk of ischemic stroke

被引:460
作者
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
机构
[1] deCODE Genet, IS-101 Reykjavik, Iceland
[2] Natl Univ Hosp Reykjavik, Reykjavik, Iceland
[3] Iceland Heart Assoc Heart Prevent Clin, Reykjavik, Iceland
[4] Hoffmann La Roche AG, Div Pharma, Preclin Res, Basel, Switzerland
关键词
D O I
10.1038/ng1245
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:131 / 138
页数:8
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