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Titolo:
Phenotyping of flavin-containing monooxygenase using caffeine metabolism and genotyping of FMO3 gene in a Korean population
Autore:
Park, CS; Chung, WG; Kang, JH; Roh, HK; Lee, KH; Cha, YN;
Indirizzi:
Inha Univ, Coll Med, Dept Pharmacol & Toxicol, Inchon 402751, South Korea Inha Univ Inchon South Korea 402751 Toxicol, Inchon 402751, South Korea Inha Univ, Coll Med, Med Toxicol Res Ctr, Inchon, South Korea Inha Univ Inchon South Korea , Med Toxicol Res Ctr, Inchon, South Korea Inha Univ, Coll Med, Dept Internal Med, Inchon, South Korea Inha Univ Inchon South Korea ed, Dept Internal Med, Inchon, South Korea
Titolo Testata:
PHARMACOGENETICS
fascicolo: 2, volume: 9, anno: 1999,
pagine: 155 - 164
SICI:
0960-314X(199904)9:2<155:POFMUC>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
FISH-ODOR SYNDROME; LIVER-MICROSOMES; N-OXIDATION; RAT-LIVER; TRIMETHYLAMINURIA; HUMANS; FAMILY; DNA;
Keywords:
caffeine; FMO; phenotypes; genotypes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Cha, YN Inha Univ, Coll Med, Dept Pharmacol & Toxicol, Inchon 402751, South Korea Inha Univ Inchon South Korea 402751 , Inchon 402751, South Korea
Citazione:
C.S. Park et al., "Phenotyping of flavin-containing monooxygenase using caffeine metabolism and genotyping of FMO3 gene in a Korean population", PHARMACOGEN, 9(2), 1999, pp. 155-164

Abstract

Flavin-containing monooxygenase (FMO) activity was determined in 82 Koreanvolunteers by taking molar concentration ratio of theobromine and caffeinepresent in the 1 h urine (between 4 and 5 h) samples collected after administration of a cup of coffee containing 110 mg of caffeine. Among 82 volunteers, there were 1.9 women and 63 men (30 smokers and 52 non-smokers), Volunteers were divided into two groups comprising low (0.53-2.99) and high (3.18-11.95) FMO activities separated by an antimode of 3.18. peripheral bloods were sampled from these volunteers and their genomic DNAs were amplified by polymerase chain reaction with oligonucleotides designed from intronic sequences of human FMO3 gene. Comparing nucleotide sequences of the amplified FMO3 gene originating from randomly selected individuals with low and high FMO activities, nine point mutations were identified in the open reading frame sequences. Among these nine mutations, three FMO3 mutant types (FMO3/Stop(148), Lys(158) and Gly(308)) were selected and correlated with FMO activities observed in our Korean population. A rare FMO3/Stop(148) mutant allele originating from FMO3/Gly(148) occurred by substitution of G442T in exon 4 and yielded a premature TGA stop codon. The stop codon was detected in one individual having the second lowest FMO activity and he had the mutation in heterozygous state. In a pedigree study, he was found to have inherited the mutation from his mother who also had a heterozygous stop codon and equally low FMO activity. In our volunteers, two other common mutations weredetected in exons 4 and 7. The one in exon 4 resulted from a G472A change eliminating a HinfI restriction site and produced an amino acid substitution from Glu(158) to Lys The other mutation in exon 7 resulted from an A923G change generating a DraII restriction site and produced a non-conservative replacement of Glu(308) to Gly. Based on the secondary structure maps of FMO3 enzyme proteins for these two mutant types, FMO3/Gly(308) mutation transformed the helix structure into a sheet shape and indicated that dysfunctional FMO3 may be produced. FMO3/Lys(158) mutation did not alter the secondary structure. Approximately 80% of volunteers with homozygous and/or heterozygous mutations on either one or two of these mutations had low FMO activities. Thus, individuals with these FMO3 gene mutations may have defective metabolic activity for many clinically used drugs and dietary plant alkaloidswhich are oxidized primarily by hepatic FMO3. Pharmacogenetics 9:155-164 (C) 1999 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 16:53:11