Ismail Shorudi Dadi - Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran & Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Me
Ramin Saravani - Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran & Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Me
Tahereh Khalili - Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran & Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Me
Saman Sargazi* - ۲: Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
Mahdi Majidpour - Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran & Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Me
Mohammad Sarhadi - Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
Shekoufeh Mirinejad - Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
Sheida Shahraki - Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
Ali Alidadi - Department of Nephrology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran & Clinical Immunology Research Center (CIRC), Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Chronic kidney disease (CKD) is a global health concern involving roughly one-tenth of developed countries' populations. The flavin-containing dimethylaniline monooxygenase ۳ (FMO۳) gene encodes an enzyme that catalyzes trimethylamine N-oxide (TMAO), a toxin in CKD sufferers. This preliminary study aims to evaluate the association between coding region variations of FMO۳, rs۲۲۶۶۷۸۲G/A (E۱۵۸K), rs۲۲۶۶۷۸۰A/G (E۳۰۸G), and rs۱۷۳۶۵۵۷G/A (V۲۵۷M), and the susceptibility to CKD. Methods: A total of ۳۵۶ participants were enrolled, including ۱۵۷ patients diagnosed with CKD and ۱۹۹ age-matched healthy individuals. Genotyping of FMO۳ gene variations was performed via PCR-RFLP and ARMS-PCR methods. Results: Our findings revealed a significant association between rs۲۲۶۶۷۸۰A/G and rs۱۷۳۶۵۵۷G/A and CKD under different genetic models. Compared to the GGG haplotype of rs۲۲۶۶۷۸۲/rs۱۷۳۶۵۵۷/rs۲۲۶۶۷۸۰, the GAG, GAA, AAG, and AAA haplotype combinations conferred an increased risk of CKD in our population. Interaction analysis revealed that some genotype combinations, including GA/AA/AA, AA/AA/AA, GA/AA/GA, and GG/AG/AA, dramatically increased CKD risk in the Iranian population. No correlation was found between FMO۳ polymorphisms and CKD stages. Conclusions: These observations highlight the potential impact of coding variants of the FMO۳ gene on the onset of CKD. Further investigations into expanded populations and diverse races are needed to confirm our findings.

Keywords: Chronic kidney disease, FMO۳, Genetic variant, Single-nucleotide polymorphism, Trimethylamine N-oxide.