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Association between ABCB1 Polymorphisms and Artesunate–Mefloquine Treatment Responses of Patients with Falciparum Malaria on the Thailand–Myanmar Border

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  • 1 Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathum Thani, Thailand;
  • 2 Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathum Thani, Thailand;
  • 3 Drug Discovery and Development Center, Thammasat University (Rangsit Campus), Pathum Thani, Thailand

Abstract.

A decrease in the clinical efficacy of a 3-day artesunate–mefloquine combination treatment was reported in the areas of multidrug-resistant Plasmodium falciparum along the Thailand–Myanmar border. The current study investigated the possible contribution of genetic polymorphisms of the three major genes encoding drug efflux transporters, ABCB1, ABCG2, and ABCC1, to responses to the aforementioned treatment in 91 patients with acute uncomplicated falciparum malaria residing along the Thailand–Myanmar border. Patients carrying homozygous mutant genotype ABCB1 c.1236C>T (TT) were found to have a three-times higher chance of successful treatment with this combination compared with other genotypes (CC and CT). Furthermore, whole blood mefloquine concentrations in these patients with the TT genotype were significantly lower than those of patients carrying the CC genotype. Patients with heterozygous mutant genotype (CT), however, were three-times more likely to experience treatment failure. No significant association was found with the ABCG2 and ABCC1 gene polymorphisms. The results suggest that ABCB1 c.1236C>T polymorphisms could be useful genetic markers for predicting responses to the 3-day artesunate–mefloquine treatment; however, studies using larger sample sizes in different malaria-endemic areas are necessary to confirm this finding. This study highlights the impact of pharmacogenetic factors on antimalarial treatment responses and the basis for the application of control policies in various malaria-endemic areas.

Author Notes

Address correspondence to Kesara Na-Bangchang, Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), 99 Moo 18 Phaholyothin Rd. Klong Luang, Pathum Thani 12120, Thailand. E-mail: kesaratmu@yahoo.com

Financial support: This study was supported by Thammasat University (Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma), Thammasat University, Thailand, and the National Research Council of Thailand. Kesara Na-Bangchang is supported by the National Research Council of Thailand (Ministry of Higher Education, Science, Research, and Innovation) under the Research Team Promotion grant (grant number 820/2563).

Authors’ addresses: Kanyarat Boonprasert, Nanthawat Kosa, Anurak Cheoymang, and Kesara Na-Bangchang, Chulabhorn International College of Medicine (CICM), Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani 12120, Thailand, E-mails: noei_noey@hotmail.com, nantha.ko@hotmail.com, anurak_ch9@yahoo.com, and kesaratmu@yahoo.com. Poonuch Muhamad, Drug Discovery Center, Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani 12120, Thailand, E-mail: nurah_ab@yahoo.com.

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