title: Incidence of dementia in relation to genetic variants at PITX2, ZFHX3, and ApoE ε4 in atrial fibrillation patients.
abstract: BACKGROUND
  Mechanisms underlying atrial fibrillation (AF) and dementia are unknown. Some genetic risk factors convey risk for AF and cerebral ischemic events. These markers may identify AF patients at risk for dementia either directly or through a gene-gene interaction with the ApoE ε4 variant, a known marker of dementia risk.
  
  
  METHODS
  Caucasian patients with AF and a subsequent dementia diagnosis (n = 112) were matched 1:2 on sex, AF onset age, and follow-up period to AF patients without dementia. AF patients with dementia and AF patients without dementia were matched 1:1 on sex and age at dementia diagnosis (n = 112). Genotyping employed Taqman real-time polymerase chain reaction. Multivariable conditional logistic regression was used to examine associations between AF/dementia groups and single nucleotide polymorphism (SNP), as well as gene-gene interactions.
  
  
  RESULTS
  In dementia patients, there was an association between the PITX2 loci and AF (rs2634073: odds ratio [OR] = 2.11; P = 0.025 and rs2200733: OR = 2.27; P = 0.029). In patients with AF, there was an association between PITX2 loci, rs2200733, and dementia (OR = 2.15, P = 0.008). There was no association between ApoE ε4 allele and AF in patients with dementia, although confirmation of the association between the carriage of ApoE ε4 allele and dementia was found (OR = 1.79; P = 0.026) in patients with AF. There were no significant interactions between ApoE ε4 allele and both the PITX2 loci and ZFHX3.
  
  
  CONCLUSIONS
  These findings support prior studies of ApoE risk of noncerebral vascular accident-related dementia/Alzheimer's risk in the Caucasians and provide support to suggest an association between PITX2-related SNPs and dementia, which may in part be attributed to silent cerebral ischemic events, a hypothesis deserving further testing.
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rollo
authors.forename: Stacey
authors.initials: S
authors.lastname: Knight
authors.forename: Heidi T
authors.initials: HT
authors.lastname: May
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Muhlestein
authors.forename: T Jared
authors.initials: TJ
authors.lastname: Bunch
authors.forename: John
authors.initials: J
authors.lastname: Carlquist
mesh_terms: D017677:Age Distribution; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015984:Causality; D015897:Comorbidity; D003704:Dementia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment; D017678:Sex Distribution; D014157:Transcription Factors / Q000235:genetics*; D014589:Utah / Q000453:epidemiology; D000097577:Homeobox Protein PITX2
chemical_list: D001057:Apolipoproteins E; D005819:Genetic Markers; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C071660:ZFHX3 protein, human
keywords: atrial fibrillation; electrophysiology-clinical