TY - JOUR
T1 - Genetic backgrounds of the Plasmodium falciparum chloroquine resistant transporter (pfcrt) alleles in Pakistan
AU - Rawasia, Wasiq Faraz
AU - Sridaran, Sankar
AU - Patel, Jaymin C.
AU - Abdallah, Joseph
AU - Ghanchi, Najia Karim
AU - Barnwell, John W.
AU - Escalante, Ananias A.
AU - Udhayakumar, Venkatachalam
AU - Beg, Mohammad Asim
N1 - Funding Information:
We gratefully acknowledge the support provided HEC-USAID Grant awarded to Dr Rumina Hasan at Aga Khan University for building this CDC-AKU collaboration (MAB) and Higher Education Commission, Government of Pakistan (NKG). We acknowledge funding support from the CDC Antimicrobial Resistance Working Group and Atlanta Research and Education Foundation (AREF) , Decatur, GA. SS was initially supported by Emerging Infectious Disease Fellowship from CDC and subsequently through AREF. AE is supported by the Grant R01GM084320 from the US National Institute of Health . We thank Dr. Tauqeer Alam for providing technical assistance for the experimental work and in supporting the data analysis and editing the manuscript. We appreciate Mr. Ira Goldman for reviewing the manuscript.
PY - 2012/3
Y1 - 2012/3
N2 - Chloroquine (CQ) resistance in Plasmodium falciparum has been associated with point mutations in the P. falciparum CQ resistance transporter gene (pfcrt). Previous studies have shown 4-5 independent origins for CQ resistant pfcrt alleles globally, two in South America, one each in Southeast Asia, Papua New Guinea (PNG) and Philippines. In Asia, at least two different alleles corresponding to amino acids 72-76 (CVIET and SVMNT) have been found. The CVIET allele originated in Southeast Asia and then spread to Asia and Africa as well. The SVMNT allele, originating from PNG, has been found in India. This study was undertaken to investigate the genetic background of the CQ resistant pfcrt haplotypes in Pakistan. We genotyped microsatellite markers surrounding the pfcrt gene (six different markers at -12.3, -4.8, -1, 1.5, 3.9, 18.8. kb) in 114 clinical isolates of P. falciparum collected from different regions in Pakistan. Microsatellite analysis showed a significant reduction in genetic variation among the mutant SVMNT pfcrt alleles when compared to wild type alleles. The predominant SVMNT haplotype found in this study shared the same microsatellite haplotype found in both PNG and India. Two isolates with CVIET haplotypes showed similar microsatellite background to those found in Africa and Asia. In conclusion, this study suggests that CQ resistant SVMNT haplotypes in India and Pakistan have a common ancestral origin similar to that of Papua New Guinean isolates.
AB - Chloroquine (CQ) resistance in Plasmodium falciparum has been associated with point mutations in the P. falciparum CQ resistance transporter gene (pfcrt). Previous studies have shown 4-5 independent origins for CQ resistant pfcrt alleles globally, two in South America, one each in Southeast Asia, Papua New Guinea (PNG) and Philippines. In Asia, at least two different alleles corresponding to amino acids 72-76 (CVIET and SVMNT) have been found. The CVIET allele originated in Southeast Asia and then spread to Asia and Africa as well. The SVMNT allele, originating from PNG, has been found in India. This study was undertaken to investigate the genetic background of the CQ resistant pfcrt haplotypes in Pakistan. We genotyped microsatellite markers surrounding the pfcrt gene (six different markers at -12.3, -4.8, -1, 1.5, 3.9, 18.8. kb) in 114 clinical isolates of P. falciparum collected from different regions in Pakistan. Microsatellite analysis showed a significant reduction in genetic variation among the mutant SVMNT pfcrt alleles when compared to wild type alleles. The predominant SVMNT haplotype found in this study shared the same microsatellite haplotype found in both PNG and India. Two isolates with CVIET haplotypes showed similar microsatellite background to those found in Africa and Asia. In conclusion, this study suggests that CQ resistant SVMNT haplotypes in India and Pakistan have a common ancestral origin similar to that of Papua New Guinean isolates.
KW - Chloroquine
KW - Drug resistance
KW - Malaria
KW - Plasmodium falciparum
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U2 - 10.1016/j.meegid.2011.11.008
DO - 10.1016/j.meegid.2011.11.008
M3 - Article
C2 - 22138496
AN - SCOPUS:84857653619
SN - 1567-1348
VL - 12
SP - 278
EP - 281
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
IS - 2
ER -