FMO3-TMAO axis modulates the clinical outcome in chronic heart-failure patients with reduced ejection fraction: evidence from an Asian population.
10.1007/s11684-021-0857-2
- Author:
Haoran WEI
1
;
Mingming ZHAO
2
,
3
,
4
;
Man HUANG
1
;
Chenze LI
1
;
Jianing GAO
5
,
6
;
Ting YU
1
;
Qi ZHANG
5
,
6
;
Xiaoqing SHEN
1
;
Liang JI
5
,
6
;
Li NI
1
;
Chunxia ZHAO
1
;
Zeneng WANG
7
;
Erdan DONG
2
,
3
,
4
;
Lemin ZHENG
5
,
8
;
Dao Wen WANG
9
Author Information
1. Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China.
2. Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital
3. NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides
4. Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China.
5. The Institute of Cardiovascular Sciences, Peking University
6. Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.
7. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
8. Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China. zhengl@bjmu.edu.cn.
9. Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China. dwwang@tjh.tjmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
chronic heart failure;
flavin monooxygenase 3;
single nucleotide polymorphism;
trimethylamine-N-oxide
- MeSH:
Carnitine;
Choline/metabolism*;
Chronic Disease;
Heart Failure/genetics*;
Humans;
Methylamines;
Oxygenases;
Prospective Studies
- From:
Frontiers of Medicine
2022;16(2):295-305
- CountryChina
- Language:English
-
Abstract:
The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
