Host candidate gene polymorphisms and associated clearance ofP. falciparumamodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon

Ali, I. M. et al. (2014) Host candidate gene polymorphisms and associated clearance ofP. falciparumamodiaquine and fansidar resistance mutants in children less than 5 years in Cameroon. Pathogens and Global Health, 108(7), pp. 323-333. (doi:10.1179/2047773214Y.0000000159)

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Abstract

Background: In this post-hoc analysis, we determined the influence of single nucleotide polymorphisms in host candidate immune genes on the outcome of drug resistant malaria in Cameroon.

Methods: Human DNA from 760 patients from a previous clinical trial was subjected to mass spectrometry-based single nucleotide polymorphism (SNP) genotyping. Allele frequencies of candidate immune genes were calculated for 62 SNPs on 17 human chromosomes for their possible involvement in clearance of drug-resistant parasites with the triple mutations of pfcrt76T, pfmdr86Y, and pfmdr1246Y (TY) and pfdhfr51I, pfdhfr59R, pfdhfr108N, and pfdhps437G (IRNG) which were determined by dotblot or PCR-restriction analysis. Differences in SNP frequencies and association analysis were carried out by comparing Chi-square odds ratios (ORs) and stratified by Mantel–Haenzel statistics. An adjusted P value (OR) <0·0008 was considered significant.

Results: Post-treatment drug failure rates were amodiaquine (36·4%); sulpadoxine/pyrimethamine-amodiaquine combination (15·4%); and sulphadoxine/pyrimethamine (18·1%). SNPs in IL22, IL-4R1, and CD36 appeared to have been associated with clearance of resistant parasites [p  =  0·017, OR (C allele):1·44, 95% CI (OR): 1·06–1·95]; [P  =  0·014, OR  =  1·31, 95% CI (OR): 1·07–1·83]; [P  =  5·78×10−5, OR  =  0·27, 95%CI (OR): 0·13–0·54], respectively, with high fever (>39°C for 48 hours) [IL-22, P  =  0·01, OR  =  1·5, 95% CI (OR): 1·8–2·1] and also in high frequency among the Fulani participants [P  =  0·006, OR  =  1·83, 95% CI (OR): 1·11–3·08)]. The CD36-1264 null allele was completely absent in the northern population.

Conclusion: Independent association of SNPs in IL22 and IL-4 with clearance of amodiaquine- and sulphadoxine/pyrimethamine-resistant parasites did not reach statistical significance, but may suggest that not all drug-resistant mutants are adversely affected by the same immune-mediated mechanisms of clearance.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ranford-Cartwright, Dr Lisa
Authors: Ali, I. M., Evehe, M.-S. B., Netongo, P. M., Atogho-Tiedeu, B., Akindeh-Nji, M., Ngora, H., Domkam, I. K., Diakite, M., Baldip, K., Ranford-Cartwright, L., Mimche, P. N., Lamb, T., and Mbacham, W. F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Pathogens and Global Health
Publisher:Maney Publishing
ISSN:2047-7724
ISSN (Online):2047-7732

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