Relationship Between CYP2C8*2 and Pfmdr1 N86Y Polymorphisms in Patients with Uncomplicated Malaria in Yaounde, Centre Region of Cameroon

Abstract

: Background: Plasmodium falciparum malaria is a major public health problem in Cameroon. It remains endemic and is the leading cause of morbidity and mortality in the most vulnerable groups, including children under five and pregnant women. The fight against plasmodium today faces not only diversity, preventive struggles, but also the spread of resistant parasites to available antimalarials. Several factors, among others, genetic factors, and the immune system predispose patients to develop resistances. The parasite's resistance to antimalarial would continue to be an obstacle to the management of malaria in Cameroon. This study aimed to determine the frequency of the mutation affecting the gene CYP2C8 ( CYP2C8 *2) and its influence on the mutation N86Y of the plasmodial gene Pfmdr1 in children under 15 years of age suffering from non-complicated malaria in Yaounde. Methods: This was a population based, retrospective study in a Cameroonian population. Archived whole blood samples collected from One hundred children infected with Plasmodium falciparum malaria were randomly selected. Blood samples spotted on filter papers were used for DNA (plasmodial and human) extraction performed by the chelex-100 method. The PfmdrI marker was established by the nested PCR and gene involved in the metabolism of antimalarial by conventional PCR. The RFLP-PCR technique allowed the detection of the polymorphism of these mutations. The restriction enzyme bclI was used for the polymorphisms of the cyp2C8 gene and the restriction enzyme AflIII for PfmdrI . Results: the mutant allele CYP2C8*2 had a frequency of 38%. For the Pfmdr1 gene, 57% of isolates were detected with the mutant 86Y. The application of the Khi2 statistical test showed that patients with the mutant allele CYP2C8*2 were more likely to be infected with the pfmdrI -86Y mutant strain (OR: 2,446; P: 0.030). Conclusion: This study reported that the mutant allele CYP2C8*2 influences the emergence of Pfmdr1 86Y mutants.