title: Dihydrofolate reductase gene intronic 19-bp deletion polymorphisms in a Japanese population.
abstract: Dihydrofolate reductase gene (DHFR) 19-bp deletion polymorphisms result in varied DHFR enzymatic activity affecting the risk for preterm delivery, spina bifida, and the efficacy of methotrexate (MTX). Ethnic differences in DHFR 19-bp polymorphisms may be responsible for the divergent findings in previous genetic studies. We compared genotype and allele frequency of DHFR intronic 19-bp deletion polymorphisms in ethnically homogenous East Asians (from Japan) and others by polymerase chain reaction assay conducted on 277 healthy Japanese individuals. The genotype distribution was as follows: wild/wild, 11.9% (n=33); wild/deletion, 40.1% (n=111); deletion/deletion, 48.0% (n=133). The frequencies of wild type and deletion alleles were 0.32 and 0.68, respectively. The obtained genotype distribution was consistent with those calculated by Hardy-Weinberg equilibrium. The genotype distribution and allele frequencies in the Japanese population were significantly different from those previously reported for other ethnic populations. Determination of intronic 19-bp deletion polymorphisms of DHFR may be useful for monitoring the efficacy and side effects of MTX for the treatment of diseases such as rheumatoid arthritis and childhood acute leukemia in the Japanese population because the frequency of the deletion allele is higher.
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Masato
authors.initials: M
authors.lastname: Horino
authors.forename: Mariko
authors.initials: M
authors.lastname: Morishita
authors.forename: Yui
authors.initials: Y
authors.lastname: Tazoe
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsuboi
authors.forename: Taiji
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kosuge
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics*; D007564:Japan / Q000208:ethnology; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D013762:Tetrahydrofolate Dehydrogenase