Author + information
- Jeffrey Rollo,
- Stacey Knight,
- Heidi May,
- Jeffrey Anderson,
- J. Muhlestein,
- Thomas Bunch and
- John Carlquist
Genetic predisposition to dementia has been strongly sought, but risk loci remain elusive. Atrial fibrillation (AF), a known risk factor for cerebrovascular accidents (CVA), was recently linked with dementia, especially in a younger population. Two chromosomal loci, 4q25 and 16q22, are associated with AF and CVA risk and may similarly predispose to dementia. Therefore, tested for an association between three known AF-risk variants, rs2200733, rs2634073 (both 4q25), and rs7193343 (16q22) and dementia. Also tested epsilon 4 allele of the ApoE gene (comprising two variants, rs429358 and rs74120) which is associated with Alzheimer's disease.
This was a retrospective, observational study using DNA from consenting patients (pts) enrolled in the Intermountain Heart Collaborative Study. All AF diagnoses preceded dementia diagnoses (including Alzheimer's) and were defined by ICD-9 codes. AF pts with dementia (n=132) were matched 1:2 by sex, AF onset age (±5 years) and follow up period (age at dementia ≤ age at last follow-up) to AF pts without dementia (n=264). A second 1:1 matching schema was performed between AF pts with dementia and dementia pts without AF (n=132) by sex and age at dementia diagnosis (AF dementia onset age ≤ Non-AF dementia onset age). Genotyping employed Taqman real-time PCR. Chi-square trend tests performed to verify associations between AF/dementia groups and SNPs.
Cases were 59.1% male with average age of AF onset at 74 years and average age of dementia at 78 in AF pts and 80 in non-AF pts. In AF pts, dementia was associated with rs2200733 (p=0.038) and rs429358 (p=0.003). However, when pts with CVA prior to dementia diagnosis were excluded from AF with dementia group, rs2200733 showed no significance with dementia (p=0.3681), yet rs429358 remained significant (p=0.001) and rs7412 became significant (p=0.006). rs2200733 (p=0.016) and rs2614073 (p=0.043) were both associated with AF in pts with dementia.
This data supports prior studies of ApoE risk of non-CVA related dementia/Alzheimer's in the general population. Furthermore, these findings suggest that association between rs2200733 and dementia maybe due to CVA in AF populations.
Poster Sessions, Expo North
Saturday, March 09, 2013, 3:45 p.m.-4:30 p.m.
Session Title: Arrhythmias: AF/SVT III
Abstract Category: 4. Arrhythmias: AF/SVT
Presentation Number: 1151-46
- 2013 American College of Cardiology Foundation