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The MSPDBL2 codon 591 polymorphism is associated with lumefantrine in vitro drug responses in Plasmodium falciparum isolates from Kilifi, Kenya.

Ochola-Oyier LI, Okombo J, Mwai L, Kiara SM, Pole L, Tetteh KK, Nzila A, Marsh K - Antimicrob. Agents Chemother. (2014)

Bottom Line: The mechanisms of drug resistance development in the Plasmodium falciparum parasite to lumefantrine (LUM), commonly used in combination with artemisinin, are still unclear.We assessed the polymorphisms of Pfmspdbl2 for associations with LUM activity in a Kenyan population.MSPDBL2 codon 591S was associated with reduced susceptibility to LUM (P = 0.04).

View Article: PubMed Central - PubMed

Affiliation: Kenya Medical Research Institute/Wellcome Trust Collaborative Research Program, Kilifi, Kenya liochola@kemri-wellcome.org.

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Linkage disequilibrium in the Pfmsp3 multigene family. The haplotypes were generated from an analysis of sequenced SNPs. Haplotypes shown are Pfmsp3 K1 and 3D7 (A), Pfmsp6 K1 and 3D7 (B), Pfmspdbl1 DBL domain AHQAIRY, ALTAIKY, and ALQAMKY (C), Pfmspdbl1 3′ DBL domain NEVRI, DKIQF, and NEIQF block 2, NGGRI and DEGIK block 3, TSV and TTG block 4, and the SPAM domain KN and EN (D), Pfmspdbl2 DBL domain AHQAIRY, ALQAIKY, and ALQAMKY (E), and Pfmspdbl2 SPAM domain 8 (F). Each column represents an SNP, each color in the column represents a different nucleotide, and each row represents an isolate sequence. The black outline depicts the allelic blocks. The columns shaded in gray are in linkage disequilibrium, and the amino acids from these polymorphisms were used to define the haplotypes. INS, number of nucleotides inserted (e.g., INS3 means 3 nucleotides); DEL, absence of sequence (i.e., a deletion).
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Figure 1: Linkage disequilibrium in the Pfmsp3 multigene family. The haplotypes were generated from an analysis of sequenced SNPs. Haplotypes shown are Pfmsp3 K1 and 3D7 (A), Pfmsp6 K1 and 3D7 (B), Pfmspdbl1 DBL domain AHQAIRY, ALTAIKY, and ALQAMKY (C), Pfmspdbl1 3′ DBL domain NEVRI, DKIQF, and NEIQF block 2, NGGRI and DEGIK block 3, TSV and TTG block 4, and the SPAM domain KN and EN (D), Pfmspdbl2 DBL domain AHQAIRY, ALQAIKY, and ALQAMKY (E), and Pfmspdbl2 SPAM domain 8 (F). Each column represents an SNP, each color in the column represents a different nucleotide, and each row represents an isolate sequence. The black outline depicts the allelic blocks. The columns shaded in gray are in linkage disequilibrium, and the amino acids from these polymorphisms were used to define the haplotypes. INS, number of nucleotides inserted (e.g., INS3 means 3 nucleotides); DEL, absence of sequence (i.e., a deletion).

Mentions: All msp3 and msp6 SNPs analyzed were in linkage disequilibrium, representing two previously defined alleles, K1 and 3D7 (Fig. 1A and B, respectively) (16, 17), therefore precluding individual SNP analysis. The activity of all the drugs tested did not differ in parasites harboring 3D7 or K1 alleles in the msp3 and msp6 genes (Table 1). The SNPs of Pfmspdbl1 and Pfmspdbl2 were used to determine the actual loci within the haplotypes associated with changes in drug responses.


The MSPDBL2 codon 591 polymorphism is associated with lumefantrine in vitro drug responses in Plasmodium falciparum isolates from Kilifi, Kenya.

Ochola-Oyier LI, Okombo J, Mwai L, Kiara SM, Pole L, Tetteh KK, Nzila A, Marsh K - Antimicrob. Agents Chemother. (2014)

Linkage disequilibrium in the Pfmsp3 multigene family. The haplotypes were generated from an analysis of sequenced SNPs. Haplotypes shown are Pfmsp3 K1 and 3D7 (A), Pfmsp6 K1 and 3D7 (B), Pfmspdbl1 DBL domain AHQAIRY, ALTAIKY, and ALQAMKY (C), Pfmspdbl1 3′ DBL domain NEVRI, DKIQF, and NEIQF block 2, NGGRI and DEGIK block 3, TSV and TTG block 4, and the SPAM domain KN and EN (D), Pfmspdbl2 DBL domain AHQAIRY, ALQAIKY, and ALQAMKY (E), and Pfmspdbl2 SPAM domain 8 (F). Each column represents an SNP, each color in the column represents a different nucleotide, and each row represents an isolate sequence. The black outline depicts the allelic blocks. The columns shaded in gray are in linkage disequilibrium, and the amino acids from these polymorphisms were used to define the haplotypes. INS, number of nucleotides inserted (e.g., INS3 means 3 nucleotides); DEL, absence of sequence (i.e., a deletion).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325780&req=5

Figure 1: Linkage disequilibrium in the Pfmsp3 multigene family. The haplotypes were generated from an analysis of sequenced SNPs. Haplotypes shown are Pfmsp3 K1 and 3D7 (A), Pfmsp6 K1 and 3D7 (B), Pfmspdbl1 DBL domain AHQAIRY, ALTAIKY, and ALQAMKY (C), Pfmspdbl1 3′ DBL domain NEVRI, DKIQF, and NEIQF block 2, NGGRI and DEGIK block 3, TSV and TTG block 4, and the SPAM domain KN and EN (D), Pfmspdbl2 DBL domain AHQAIRY, ALQAIKY, and ALQAMKY (E), and Pfmspdbl2 SPAM domain 8 (F). Each column represents an SNP, each color in the column represents a different nucleotide, and each row represents an isolate sequence. The black outline depicts the allelic blocks. The columns shaded in gray are in linkage disequilibrium, and the amino acids from these polymorphisms were used to define the haplotypes. INS, number of nucleotides inserted (e.g., INS3 means 3 nucleotides); DEL, absence of sequence (i.e., a deletion).
Mentions: All msp3 and msp6 SNPs analyzed were in linkage disequilibrium, representing two previously defined alleles, K1 and 3D7 (Fig. 1A and B, respectively) (16, 17), therefore precluding individual SNP analysis. The activity of all the drugs tested did not differ in parasites harboring 3D7 or K1 alleles in the msp3 and msp6 genes (Table 1). The SNPs of Pfmspdbl1 and Pfmspdbl2 were used to determine the actual loci within the haplotypes associated with changes in drug responses.

Bottom Line: The mechanisms of drug resistance development in the Plasmodium falciparum parasite to lumefantrine (LUM), commonly used in combination with artemisinin, are still unclear.We assessed the polymorphisms of Pfmspdbl2 for associations with LUM activity in a Kenyan population.MSPDBL2 codon 591S was associated with reduced susceptibility to LUM (P = 0.04).

View Article: PubMed Central - PubMed

Affiliation: Kenya Medical Research Institute/Wellcome Trust Collaborative Research Program, Kilifi, Kenya liochola@kemri-wellcome.org.

Show MeSH
Related in: MedlinePlus