title: Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar.
abstract: Dihydrofolate reductase (DHFR; EC1.5.1.3) is a known target enzyme for antifolate agents, which are used as alternative chemotherapeutics for chloroquine-resistant malaria. Mutations in the dhfr gene of Plasmodium vivax are thought to be associated with resistance to the antifolate drugs. In this study, we have analyzed genetic variations in the dhfr genes of clinical isolates of P. vivax (n=21) in Myanmar, to monitor antifolate resistance in this country. Sequence variations within the entire dhfr gene were highly restricted to codons from 57 to 117, and the GGDN tandem repeat region. Double (S58R and S117N/T) or quadruple mutations (F57L/I, S58R, T61M, and S117N/T), which may be closely related to the drug resistance, were recognized in most of the isolates (20/21 cases). Our results suggest that antifolate-resistant P. vivax is becoming widespread in Myanmar, as it also is in the neighboring countries in Southeast Asia. It appears that the drug resistance situation may be worsening in the country.
authors.affiliation: Department of Molecular Parasitology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Byoung-Kuk
authors.initials: BK
authors.lastname: Na
authors.forename: Hyeong-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Sung-Ung
authors.initials: SU
authors.lastname: Moon
authors.forename: Tae-Suk
authors.initials: TS
authors.lastname: In
authors.forename: Khin
authors.initials: K
authors.lastname: Lin
authors.forename: Maung
authors.initials: M
authors.lastname: Maung
authors.forename: Gyung-Tae
authors.initials: GT
authors.lastname: Chung
authors.forename: Jong-Koo
authors.initials: JK
authors.lastname: Lee
authors.forename: Tong-Soo
authors.initials: TS
authors.lastname: Kim
authors.forename: Yoon
authors.initials: Y
authors.lastname: Kong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003062:Codon; D014644:Genetic Variation; D006801:Humans; D016780:Malaria, Vivax / Q000469:parasitology; D008969:Molecular Sequence Data; D002052:Myanmar; D010966:Plasmodium vivax / Q000235:genetics*; D016415:Sequence Alignment; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D003062:Codon; D013762:Tetrahydrofolate Dehydrogenase