title: Phosphodiesterase 4D and 5-lipoxygenase activating protein in ischemic stroke.
abstract: Risk for ischemic stroke is mediated by both environmental and genetic factors. Although several environmental exposures have been implicated, relatively little is known about the genetic basis of predisposition to this disease. Recent studies in Iceland identified risk polymorphisms in two putative candidate genes for ischemic stroke: phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5AP). A collection of North American sibling pairs concordant for ischemic stroke and two cohorts of prospectively ascertained North American ischemic stroke cases and control subjects were used for evaluation of PDE4D and ALOX5AP. Although no evidence supported linkage of ischemic stroke with either of the two candidate genes, single-nucleotide polymorphisms and haplotypic associations were observed between PDE4D and ischemic stroke. There was no evidence of association between variants of ALOX5AP and ischemic stroke. These data suggest that common variants in PDE4D may contribute to the genetic risk for ischemic stroke in multiple populations.
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA. meschia.james@mayo.edu
authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Brott
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brown
authors.forename: Richard
authors.initials: R
authors.lastname: Crook
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.forename: Brett
authors.initials: B
authors.lastname: Kissela
authors.forename: W Mark
authors.initials: WM
authors.lastname: Brown
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: L Douglas
authors.initials: LD
authors.lastname: Case
authors.forename: E Whitney
authors.initials: EW
authors.lastname: Evans
authors.forename: Stephen
authors.initials: S
authors.lastname: Hague
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: John
authors.initials: J
authors.lastname: Hardy
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D058927:5-Lipoxygenase-Activating Proteins; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002874:Chromosome Mapping / Q000379:methods; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003710:Demography; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors; D035781:Siblings
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human