title: A large-sample assessment of possible association between ischaemic stroke and rs12188950 in the PDE4D gene.
abstract: Previous reports have shown ambiguous findings regarding the possible associations between ischaemic stroke (IS) and single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) gene region. The SNP rs12188950 (or SNP45) has often been studied in this context. We performed a multi-centre study involving a large sample of 2599 IS patients and 2093 control subjects from the south and west regions of Sweden to replicate previous studies regarding IS risk and rs12188950. Subjects from Lund Stroke Register (LSR), Malmö Diet and Cancer Study (MDC) and Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) were enroled. Subgroups of participants with hypertension and participants <55 years of age, as well as the TOAST subgroups large vessel disease, small vessel disease and cardioembolism, were also assessed. Univariate odds ratios (ORs) and ORs controlling for hypertension, diabetes and current smoking were calculated. We additionally performed a meta-analysis including 10,500 patients and 10,102 control subjects from 17 publications (including the present study). When assessing pooled data from LSR, MDC and SAHLSIS we obtained no association between IS and rs12188950 for all participants (OR=0.93; 95% confidence interval (CI): 0.83-1.05). Significant associations were not found for hypertensive participants or participants with age <55, or when separately evaluating patients from the three different TOAST subgroups. The meta-analysis showed no significant overall estimate (OR=0.96; 95% CI: 0.89-1.04) with significant heterogeneity for random effect (P=0.042). No effect from rs12188950 on IS was found from either our pooled multi-centre data or the performed meta-analysis. We did not find any association between the examined subgroups and rs12188950 either.
authors.affiliation: Department of Clinical Sciences, Neurology, Lund University, Lund, Sweden. hakan.lovkvist@skane.se
authors.forename: Håkan
authors.initials: H
authors.lastname: Lövkvist
authors.forename: Sandra
authors.initials: S
authors.lastname: Olsson
authors.forename: Peter
authors.initials: P
authors.lastname: Höglund
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Christina
authors.initials: C
authors.lastname: Jern
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: J Gustav
authors.initials: JG
authors.lastname: Smith
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gunnar
authors.initials: G
authors.lastname: Andsberg
authors.forename: Hossein
authors.initials: H
authors.lastname: Delavaran
authors.forename: Katarina
authors.initials: K
authors.lastname: Jood
authors.forename: Ulf
authors.initials: U
authors.lastname: Kristoffersson
authors.forename: Holger
authors.initials: H
authors.lastname: Luthman
authors.forename: Bo
authors.initials: B
authors.lastname: Norrving
authors.forename: Arne
authors.initials: A
authors.lastname: Lindgren
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000235:genetics*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D060005:Genotyping Techniques; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007511:Ischemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D020521:Stroke / Q000235:genetics*; D013548:Sweden; D055815:Young Adult
chemical_list: D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human