title: Association of ZFHX3 gene variation with atrial fibrillation, cerebral infarction, and lung thromboembolism: An autopsy study.
abstract: OBJECTIVE
  We aimed to study a single nucleotide polymorphism (SNP), rs2106261, in the transcription factor gene, ZFHX3, in atrial fibrillation (AF) and other related phenotypes by phenome scanning in a Japanese population.
  
  
  METHODS
  We retrieved consecutive autopsy data (n=2433, mean age=80 years) from the Japanese SNP database for geriatric diseases (JG-SNP). Clinical data, including an AF diagnosis, were collected from medical charts. Genotyping was performed with the DNA chip method. We also analyzed 42 pathological and 26 clinical phenotypes, including cerebral infarctions (CIs) and lung thromboembolisms (LTs), diagnosed by macroscopic inspection during the autopsy.
  
  
  RESULTS
  Among the 2433 patients with available data, 18.6% had AF, 29.4% had CI, and 4.9% had LT phenotypes. The A allele of the rs2106261 SNP was significantly associated with AF, after adjusting for age, sex, diabetes, hypertension, and smoking (AA+AG/GG, OR=1.51, 95%CI: 1.16-1.97, p=0.002). In the entire cohort, CI was not associated with rs2106261 (p=0.14). However, among patients under 80 years old, rs2106261 was significantly associated with CI (AA+AG/GG, OR=1.57, 95%CI: 1.09-2.26, p=0.01). LT was also associated with rs2106261 (AA+AG/GG, OR=1.99, 95%CI: 1.31-3.01, p=0.001). Associations between rs2106261 and CI and LT remained positive after adjusting for the presence of AF, which indicated that this SNP variant might serve as an independent risk marker.
  
  
  CONCLUSIONS
  We showed that the ZFHX3 polymorphism, rs2106261 (A allele), was a risk marker for AF and AF-related phenotypes. The roles of this variant in the development of AF and its related phenotypes warrant further investigation.
authors.affiliation: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Khin Thet Thet
authors.initials: KTT
authors.lastname: Zaw
authors.affiliation: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Data Science Department, JCRAC Data Center, Clinical Research Center, National Medical Research Center Hospital, Tokyo, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kaung Si
authors.initials: KS
authors.lastname: Thu
authors.affiliation: Department of Medical Informatics, Center of Information, Jichii Medical University, Tochigi, Japan.
authors.forename: Makiko Naka
authors.initials: MN
authors.lastname: Mieno
authors.affiliation: Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan; Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.affiliation: Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Seijiro
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Bioinformational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Department of Biofunctional Informatics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sasano
authors.affiliation: Department of Moleculo-genetic Sciences, Division of Biomedical Laboratory Sciences, Molecular Pathophysiology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.affiliation: Department of Clinical Laboratory, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: muramatsu.epi@mri.tmd.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000235:genetics*; D001344:Autopsy; D002544:Cerebral Infarction / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011655:Pulmonary Embolism / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C071660:ZFHX3 protein, human
keywords: ATBF1; Atrial fibrillation; Cerebral infarction; Lung thromboembolism; Single nucleotide polymorphism