Khin Thet Thet Zaw1, Noriko Sato1, Shinobu Ikeda2, Kaung Si Thu1, Makiko Naka Mieno3, Tomio Arai4, Seijiro Mori5, Tetsushi Furukawa6, Tetsuo Sasano7, Motoji Sawabe8, Masashi Tanaka9, Masaaki Muramatsu10. 1. Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. 2. Data Science Department, JCRAC Data Center, Clinical Research Center, National Medical Research Center Hospital, Tokyo, Japan. 3. Department of Medical Informatics, Center of Information, Jichii Medical University, Tochigi, Japan. 4. Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan; Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. 5. Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan. 6. Department of Bioinformational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. 7. Department of Biofunctional Informatics, Tokyo Medical and Dental University, Tokyo, Japan. 8. 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. 9. Department of Clinical Laboratory, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan. 10. Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: muramatsu.epi@mri.tmd.ac.jp.
Abstract
AIM: 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. METHOD: 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. RESULT: 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. CONCLUSION: 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.
AIM: 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. METHOD: 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. RESULT: 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. CONCLUSION: 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: Lindsay J Young; Steve Antwi-Boasiako; Joel Ferrall; Loren E Wold; Peter J Mohler; Mona El Refaey Journal: Life Sci Date: 2022-04-03 Impact factor: 6.780
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