Novel variants and haplotypes of human <i>flavin-containing monooxygenase 3</i> gene associated with Japanese subjects suffering from trimethylaminuria

Shimizu, Makiko; Yoda, Hiromi; Igarashi, Narumi; Makino, Miki; Tokuyama, Emi; Yamazaki, Hiroshi

doi:10.1080/00498254.2018.1539279

Cited by 12 publications

(5 citation statements)

References 30 publications

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“…Among the forty-seven FMO3 variants found in the updated database in the current study, one novel stop codon mutation (p.Gln427Ter), one novel frameshift mutation (p.Lys416SerfsTer72), and 19 novel amino-acid-substituted FMO3 variants were identified in the whole-genome sequence data in the updated 38K JPN database (Table 1). These were already tested variants FMO3 p.Phe43Ile (Shimizu et al, 2015), p.Pro153GlnfsTer14 (Shimizu et al, 2019b), and p.Pro282Leu (Shimizu et al, 2019a) in addition. Among the novel 19 amino-acid-substituted FMO3 variants, FMO3 p.Met260Lys was recently reported in a compound variant found during phenotype-genotype analysis (Shimizu et al, 2023).…”

Section: New Fmo3 Variantsmentioning

confidence: 99%

Variants of Flavin-Containing Monooxygenase 3 Found in Subjects in an Updated Database of Genome Resources

et al. 2023

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Single-nucleotide substitutions of human flavin-containing monooxygenase 3 (FMO3) identified in the whole-genome sequences of the updated Japanese population reference panel (now containing 38,000 subjects) were investigated. In this study, 2 stop codon mutations, 2 frameshifts, and 43 amino-acid-substituted FMO3 variants were identified. Among these 47 variants, 1 stop codon mutation, 1 frameshift, and 24 substituted variants were already recorded in the National Center for Biotechnology Information database. Functionally impaired FMO3 variants are known to be associated with the metabolic disorder trimethylaminuria; consequently, the enzymatic activities of the 43 substituted FMO3 variants were investigated. Twenty-seven recombinant FMO3 variants expressed in bacterial membranes had similar activities toward trimethylamine N-oxygenation (~75-125%) to that of wild-type FMO3 (98 min -1 ). However, 6 recombinant FMO3 variants (Arg51Gly, Val283Ala, Asp286His, Val382Ala, Arg387His, and Phe451Leu) had moderately decreased (≈50%) activities toward trimethylamine N-oxygenation, and 10 recombinant FMO3 variants (Gly11Asp,

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Section: New Fmo3 Variantsmentioning

confidence: 99%

Variants of Flavin-Containing Monooxygenase 3 Found in Subjects in an Updated Database of Genome Resources

et al. 2023

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“…Although TMAU incidence is uncertain, it is classified as a rare autosomal recessive disease 4 . FMO3 loss of function results in failure of smelly TMA oxidation and its excretion in body fluids to produce the “rotten fish odour,” typical of the TMAU phenotype 5‐7 . This odour is often wrongly attributed to lack of personal hygiene.…”

Section: What Is Known and Objectivesmentioning

confidence: 99%

Antiretroviral treatment leading to secondary trimethylaminuria: Genetic associations and successful management with riboflavin

et al. 2020

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What is known and objective Trimethylaminuria is a metabolic disorder characterized by excessive excretion of trimethylamine in body fluids following FMO3 gene mutations. Secondary forms of the disease may be due to consumption of trimethylamine precursor‐rich foods or metabolism of some xenobiotics. Case summary A HIV patient developed secondary trimethylaminuria following antiretroviral treatment. Riboflavin supplementation ameliorated his phenotype. 1H‐NMR confirmed increased urine level of TMA. Several genes involved in choline catabolism harboured missense mutations. Riboflavin supplement improved enzymatic activity of mutated enzymes promoting TMA clearance. What is new and conclusion Antiretrovirals may increase the concentration of TMA precursors. The present study reports antiretroviral treatment as risk factor for such secondary trimethylaminuria. Riboflavin is an effective treatment.

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“…Moreover, previous studies have reported genetic polymorphisms of FMO3 that affect the enzyme activity and plasma concentrations of certain medications, and diseases such as trimethylaminuria (6)(7)(8). of these polymorphisms, the c.855c>T (n285n, rs909530), c.441c>T (S147S, rs1800822), c.923a>G (e308G, rs2266780) and c.472G>a (e158K, rs2266782) mutations are commonly detected single nucleotide polymorphisms (SnPs) in east asian populations (9)(10)(11)(12). considering their clinical importance and prevalence, there is a need to investigate the differences in the allelic frequencies of these polymorphisms between various ethnic groups and develop a reliable method for such analysis, which could be applied for optimal subject group targeting in clinical practice (8).…”

Section: Introductionmentioning

confidence: 99%

Rapid detection ofFMO3single nucleotide polymorphisms using a pyrosequencing method

Park

Kim

et al. 2021

Mol Med Rep

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The present study aimed to develop a reliable pyrosequencing method to detect four single nucleotide polymorphisms (SnPs) of the flavin-containing monooxygenase 3 (FMO3) gene and to compare the ethnic differences in their allelic frequencies. The pyrosequencing method was used to detect four FMO3 SnPs, namely, c.855c>T (n285n, rs909530), c.441c>T (S147S, rs1800822), c.923a>G (e308G, rs2266780) and c.472G>a (e158K, rs2266782). The allelic frequencies of these SnPs in 122 unrelated Korean subjects were as follows: i) 44.7% for c.855c>T; ii) 23.4% for c.441c>T; iii) 23.0% for c.923a>G; and iv) 27.1% for c.472G>a. linkage disequilibrium (ld) analysis revealed that the SnPs c.923a>G and c.472G>a exhibited a strong ld (d'=0.8289, r 2 =0.5332). in conclusion, the pyrosequencing method developed in this study was successfully applied to detect the c.855c>T, c.441c>T, c.923a>G and c.472G>a SnPs of FMO3.

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Novel variants and haplotypes of human flavin-containing monooxygenase 3 gene associated with Japanese subjects suffering from trimethylaminuria

Cited by 12 publications

References 30 publications

Variants of Flavin-Containing Monooxygenase 3 Found in Subjects in an Updated Database of Genome Resources

Variants of Flavin-Containing Monooxygenase 3 Found in Subjects in an Updated Database of Genome Resources

Antiretroviral treatment leading to secondary trimethylaminuria: Genetic associations and successful management with riboflavin

Rapid detection ofFMO3single nucleotide polymorphisms using a pyrosequencing method

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