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Titolo:
Phenotypes of flavin-containing monooxygenase activity determined by ranitidine N-oxidation are positively correlated with genotypes of linked FMO3 gene mutations in a Korean population
Autore:
Kang, JH; Chung, WG; Lee, KH; Park, CS; Kang, JS; Shin, IC; Roh, HK; Dong, MS; Baek, HM; 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, Med Toxicol Res Ctr, Inchon 402751, South Korea Inha Univ Inchon South Korea 402751 Res Ctr, Inchon 402751, South Korea Hanyang Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Hanyang Univ Seoul South Korea Med, Dept Pharmacol, Seoul, South Korea Inha Univ Hosp, Dept Internal Med, Inchon, South Korea Inha Univ Hosp Inchon South Korea ept Internal Med, Inchon, South Korea Inha Univ Hosp, Poison Ctr, Inchon, South Korea Inha Univ Hosp Inchon South Korea Hosp, Poison Ctr, Inchon, South Korea Korea Univ, Grad Sch Biotechnol, Seoul, South Korea Korea Univ Seoul South Korea v, Grad Sch Biotechnol, Seoul, South Korea
Titolo Testata:
PHARMACOGENETICS
fascicolo: 1, volume: 10, anno: 2000,
pagine: 67 - 78
SICI:
0960-314X(200002)10:1<67:POFMAD>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
FISH-ODOR SYNDROME; ADULT HUMAN LIVER; EXPRESSION; ENZYMES; TRIMETHYLAMINURIA; METABOLISM; MICROSOMES; FORM-3; CDNA;
Keywords:
FMO3; ranitidine; phenotype; genotype; linkage; Korean;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
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:
J.H. Kang et al., "Phenotypes of flavin-containing monooxygenase activity determined by ranitidine N-oxidation are positively correlated with genotypes of linked FMO3 gene mutations in a Korean population", PHARMACOGEN, 10(1), 2000, pp. 67-78

Abstract

A non-invasive mine analysis method to determine the in-vivo flavin-containing monooxygenase (FMO) activity catalysing N-oxidation of ranitidine (RA)was developed and used to phenotype a Korean population. FMO activity was assessed by the molar concentration ratio of RA and RANG in the bulked 8 h urine. This method was used to determine the FMO phenotypes of 210 Korean volunteers (173 men and 37 women, 110 nonsmokers and 100 smokers), Urinary RA/RANO ratio, representing the metabolic ratio and the reciprocal index of FMO activity, ranged from 5.67-27.20 (4.8-fold difference) and was not different between men and women (P = 0.76) or between smokers and nonsmokers (P= 0.50). The frequencies of RA/RANO ratios were distributed in a trimodal fashion. Among the 210 Korean subjects, 93 (44.3%) were fast metabolizers, 104 (49.5%) were intermediate metabolizers and 13 (6.2%) were slow metabolizers. Subsequently, the relationship between the ranitidine N-oxidation phenotypes and FMO3 genotypes, determined by the presence of two previously identified mutant alleles (Glu158Lys: FMO3/Lys(158) and Glu308Gly: FMO3/Gly(308) alleles) commonly found in our Korean population was examined. The results showed that subjects who were homozygous and heterozygous for either one or both of the FMO3/Lys(158) and FMO3/Gly(308) mutant alleles had significantly lower in-vivo FMO activities than those with homozygous wild-type alleles (FMO3/Glu(158) and FMO3/Glu(308)) (P < 0.001, Mann-Whitney U-test). Furthermore, the FMO activities of subjects with either FMO3/Lys(158) or FMO3/Gly(308) mutant alleles were almost identical to those having both FMO3 mutant alleles (FMO3/Lys(308) and FMO3/Gly(308)), These two mutant alleles located, respectively, at exons 4 and 7 in the FMO3 gene appeared to be strongly linked by cis-configuration in Koreans, Therefore, we concluded that presence of FMO3/Lys(158) and FMO3/Gly(308) mutant alleles in FMO3 gene is responsible for the low ranitidine N-oxidation (FMO3 activity) in our Koreanpopulation. Pharmacogenetics 10:67-78 (C) 2000 Lippincott Williams & Wilkins.

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Documento generato il 19/01/20 alle ore 05:59:19