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) (21254 C>A and 24006 A>G) causing amino acid substitutions, Thr²⁰¹Lys in exon 5 and Met²⁶⁰Val in exon 6, respectively. The Thr²⁰¹Lys and Met²⁶⁰Val also presented together with known SNPs (Glu¹⁵⁸Lys-Glu³⁰⁸Gly and Val²⁵⁷Met, respectively) in the same alleles of the FMO3 gene to form novel haplotypes. A SNP (30398 C>T) in the FMO3 gene causing a stop codon at Arg⁵⁰⁰ 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′.