Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar.
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.
Na
Byoung-Kuk
BK
Department of Molecular Parasitology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Lee
Hyeong-Woo
HW
Moon
Sung-Ung
SU
In
Tae-Suk
TS
Lin
Khin
K
Maung
Maung
M
Chung
Gyung-Tae
GT
Lee
Jong-Koo
JK
Kim
Tong-Soo
TS
Kong
Yoon
Y
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*
D003062:Codon; D013762:Tetrahydrofolate Dehydrogenase