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

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.

Automated summary

This study found that circulating TMAO levels were higher in Kurdish patients with NAFLD, and its presence may be correlated with the specific genotype -2177G>C of FMO3.