INTRODUCTION: 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.
INTRODUCTION: 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 AFpatients 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 AFpatients without dementia. AFpatients with dementia and AFpatients 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 dementiapatients, 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: T Jared Bunch; Heidi T May; Tami L Bair; Brian G Crandall; Michael J Cutler; John D Day; Victoria Jacobs; Charles Mallender; Jeffrey S Osborn; Scott M Stevens; J Peter Weiss; Scott C Woller Journal: J Am Heart Assoc Date: 2016-07-11 Impact factor: 5.501
Authors: Nikolaos Dagres; Tze-Fan Chao; Guilherme Fenelon; Luis Aguinaga; Daniel Benhayon; Emelia J Benjamin; T Jared Bunch; Lin Yee Chen; Shih-Ann Chen; Francisco Darrieux; Angelo de Paola; Laurent Fauchier; Andreas Goette; Jonathan Kalman; Lalit Kalra; Young-Hoon Kim; Deirdre A Lane; Gregory Y H Lip; Steven A Lubitz; Manlio F Márquez; Tatjana Potpara; Domingo Luis Pozzer; Jeremy N Ruskin; Irina Savelieva; Wee Siong Teo; Hung-Fat Tse; Atul Verma; Shu Zhang; Mina K Chung; William-Fernando Bautista-Vargas; Chern-En Chiang; Alejandro Cuesta; Gheorghe-Andrei Dan; David S Frankel; Yutao Guo; Robert Hatala; Young Soo Lee; Yuji Murakawa; Cara N Pellegrini; Claudio Pinho; David J Milan; Daniel P Morin; Elenir Nadalin; George Ntaios; Mukund A Prabhu; Marco Proietti; Lena Rivard; Mariana Valentino; Alena Shantsila Journal: J Arrhythm Date: 2018-03-23