title: Genetic variants associated with myocardial infarction in the PSMA6 gene and Chr9p21 are also associated with ischaemic stroke.
abstract: BACKGROUND
  Ischaemic stroke shares common traditional risk factors with coronary artery disease (CAD) and myocardial infarction (MI). This study evaluated whether genetic risk factors for CAD and MI also affect susceptibility to ischaemic stroke in Caucasians and African Americans.
  
  
  METHODS
  Included in the study were a Caucasian series (713 ischaemic stroke patients, 708 controls) and a small African American series (166 ischaemic stroke patients, 117 controls). Twenty single-nucleotide polymorphisms (SNPs) previously shown to be associated with CAD or MI were genotyped and assessed for association with ischaemic stroke and ischaemic stroke subtypes using odds ratios (ORs) from multivariable logistic regression models.
  
  
  RESULTS
  In Caucasians, four SNPs on chromosome 9p21 were significantly associated with risk of cardioembolic stroke, the strongest of which was rs1333040 (OR 1.55, P = 0.0007); similar but weaker trends were observed for small vessel stroke, with no associations observed regarding large vessel stroke. Chromosome 9p21 SNPs were also associated with risk of ischaemic stroke in African Americans (rs1333040, OR 0.65, P = 0.023; rs1333042, OR 0.55, P = 0.070; rs2383207, OR 0.55, P = 0.070). The PSMA6 SNP rs1048990 on chromosome 14q13 was associated with overall ischaemic stroke in both Caucasians (OR 0.80, P = 0.036) and African Americans (OR 0.31, P = 0.020).
  
  
  CONCLUSIONS
  Our results provide evidence that chromosome 9p21 variants are associated with cardioembolic ischaemic stroke in Caucasians and with overall ischaemic stroke in African Americans. The PSMA6 variant rs1048990 also appears to affect susceptibility to ischaemic stroke in both populations. These findings require validation, particularly the preliminary findings regarding African Americans given the small size of that series.
authors.affiliation: Biostatistics Unit, Mayo Clinic, Jacksonville, FL 32224, USA. heckman.michael@mayo.edu
authors.forename: M G
authors.initials: MG
authors.lastname: Heckman
authors.forename: A I
authors.initials: AI
authors.lastname: Soto-Ortolaza
authors.forename: N N
authors.initials: NN
authors.lastname: Diehl
authors.forename: S
authors.initials: S
authors.lastname: Rayaprolu
authors.forename: T G
authors.initials: TG
authors.lastname: Brott
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: J F
authors.initials: JF
authors.lastname: Meschia
authors.forename: O A
authors.initials: OA
authors.lastname: Ross
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D020521:Stroke / Q000150:complications / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C465641:PSMA6 protein, human; D046988:Proteasome Endopeptidase Complex