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Possible correlation between high circulatory levels of trimethylamine-N-oxide and 2177G>C polymorphisms of hepatic flavin containing monooxygenase 3 in Kurdish Population with non-alcoholic fatty liver disease

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Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disorder with complicated pathophysiology. Trimethylamine-N-oxide (TMAO) has been thought to be correlated with the pathogenesis of NAFLD. The single nucleotide polymorphisms (SNPs) of hepatic flavin-containing monooxygenase 3 (FMO3) regulate the concentration of TMAO. This case-control study investigated the plasma levels of TMAO as well as its possible correlation with the frequency of specific genotype of FMO3 (-2650C>G, -2543T>A, -2177G>C, -2589C>T, -2106G>A polymorphisms) in Kurdish patients with NAFLD.

Methods and Results

In 85 confirmed NAFLD patients and 30 healthy individuals, triglycerides (TG), total cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. TMAO was also measured using the LC–MS/MS method. High-resolution melting analysis was applied to determine FMO3 genotypes. Plasma TMAO levels were significantly higher in patients (p = 0.030). A CC genotype with a frequency of 12.9% for SNP -2177G>C was found in Kurdish NAFLD patients. The distribution of the GC genotype was also significantly different (p = 0.017).

Conclusions

The current results provide documentation for high circulatory levels of TMAO and its possible correlation with the presence of the specific genotype -2177G>C FMO3 in Kurdish NAFLD patients.

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Acknowledgements

This work, as a MSc student’s thesis, was supported financially by vice chancellor in research of Kurdistan University of Medical Sciences [Grant Numbers 1397/237-97.10.23]. This study was entirely performed at the Tohid hospital and laboratories of Kurdistan University of Medical Sciences. We thank strategic technologies laboratory network of Iran and the centres of Cellular and Molecular Research and Liver& Digestive Research of Kurdistan University of Medical Sciences for their valuable assistance. We also thank all those who helped us as well as all patients and healthy subjects participated in this research.

Funding

This study was conducted as a dissertation of a master’s student in clinical biochemistry. It was supported financially by vice chancellor in research of Kurdistan University of Medical Sciences [grant numbers 1397/237 − 97.10.23].

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Authors and Affiliations

  1. Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Mohammad Moradzad & Dana Ghaderi

  2. Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Mohammad Moradzad, Mohammad Abdi & Zakaria Vahabzadeh

  3. Liver & Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Farshad Sheikh Esmaeili, Khaled Rahmani & Mohammad Raman Moloudi

  4. Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Zakaria Vahabzadeh

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  1. Mohammad Moradzad
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Contributions

Mohammad Moradzad carried out the sample collection, all laboratory works, and final report preparation. Mohammad Abdi assisted with HRM analysis and manuscript preparation. Farshad Sheikh Esmaeili as a gastroenterologist helped to introduce and confirm NAFLD patients and healthy individuals. Dana Ghaderi helped with sample collection. Khaled Rahmani provided assistance for statistical analysis. Mohammad Raman Moloudi helped as an advisor. Zakaria Vahabzadeh carried out the design, supervised the study, and prepared the manuscript. The manuscript’s contents have been read and approved by all authors. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Zakaria Vahabzadeh.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Medical Ethics Committee of Kurdistan University of Medical Science.and with the 1964 Helsinki declaration. All subjects entered the study with full knowledge of the research project and gave informed written consent to participate. Ethics were fully observed in all protocols. The study protocol was approved by the Medical Ethics Committee of Kurdistan University of Medical Science under the code IR.MUK.REC.1397/237.

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Informed consent was obtained from all individual participants included in the study.

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Moradzad, M., Abdi, M., Sheikh Esmaeili, F. et al. Possible correlation between high circulatory levels of trimethylamine-N-oxide and 2177G>C polymorphisms of hepatic flavin containing monooxygenase 3 in Kurdish Population with non-alcoholic fatty liver disease. Mol Biol Rep 49, 5927–5937 (2022). https://doi.org/10.1007/s11033-022-07375-4

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