title: Three novel single nucleotide polymorphisms of the FMO3 gene in a Japanese population.
abstract: We sequenced all exons and exon-intron junctions of the flavin-containing monooxygenase 3 (FMO3) gene from 2 Japanese individuals and their family members, who were case subjects that showed low FMO3 metabolic capacity among a population of self-reported trimethylaminuria Japanese volunteers. We found two novel single nucleotide polymorphisms (SNPs) (21,254 C>A and 24,006 A>G) causing amino acid substitutions, Thr(201)Lys in exon 5 and Met(260)Val in exon 6, respectively. The Thr(201)Lys and Met(260)Val also presented together with known SNPs (Glu(158)Lys-Glu(308)Gly and Val(257)Met, respectively) in the same alleles of the FMO3 gene to form novel haplotypes. A SNP (30,398 C>T) in the FMO3 gene causing a stop codon at Arg(500) in exon 9 was also discovered. These sequences are as follows: 1) SNP, 060116Shimizu001; GENE NAME, FMO3; ACCESSION NUMBER, AL021026; LENGTH, 25 base; 5'-GTGATATTGCCAC/AAGAACTCAGCCG-3'. 2) SNP, 060116Shimizu002; GENE NAME, FMO3; ACCESSION NUMBER, AL021026; LENGTH, 25 base; 5'-TAC(G/A)TGAAGCAGA/GTGAATGCAAGAT-3'. 3) SNP, 060116Shimizu003; GENE NAME, FMO3; ACCESSION NUMBER, AL021026; LENGTH, 25 base; 5'-CCCATGCAGACAC/TGAGTGGTCGGGA-3'.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Haruka
authors.initials: H
authors.lastname: Fujita
authors.forename: Takahiko
authors.initials: T
authors.lastname: Aoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000652:urine; D008744:Methylamines / Q000652:urine; D009154:Mutation / Q000235:genetics; D010105:Oxygenases / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D008744:Methylamines; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); C023336:trimethylamine