| Peer-Reviewed

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

Received: 23 May 2022    Accepted: 15 June 2022    Published: 30 June 2022
Views:       Downloads:
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.

Published in American Journal of Biomedical and Life Sciences (Volume 10, Issue 3)
DOI 10.11648/j.ajbls.20221003.16
Page(s) 97-101
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Resistance, Pfmdr1, Plasmodium Falciparum, Antimalarial Metabolism, CYP2C8

References
[1] WHO, "Malaria Report," 2020. [Online]. Available: https://apps.who.int/iris/rest/bitstreams/1262394/retrieve. [Accessed 15 March 2021].
[2] CDC, "CDC - Malaria Parasites - About," 16 July 2020. [Online]. Available: https://www.cdc.gov/malaria/about/biology/parasites.html. [Accessed 24 7 2020].
[3] Bosman, P., Stassijns, J., Nackers, F., Canier, L., Kim, N., Khim, S., … Kindermans, J. M. (2014). Plasmodium prevalence and artemisinin-resistant falciparum malaria in Preah Vihear Province Cambodia: A cross-sectional population-base stud. Malaria Journal, 13 (1), 1–9.
[4] Ibraheem, Z. O., Abd Majid, R., Noor, S. M., Sedik, H. M., & Basir, R. (2014). Role of Different Pf crt and Pf mdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum. Malaria Research and Treatment, 2014 (Lm), 1–17.
[5] Price, R. N., Uhlemann, A., Brockman, A., Mcgready, R., Ashley, E., Phaipun, L., … Krishna, S. (2015). Europe PMC Funders Group Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number, 364 (9432), 438–447.
[6] Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM. Identification of human cytochrome P (450)s that metabolise antiparasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol 2003; 59: 429–42.
[7] Ribeiro V, Cavaco I. Pharmacogenetics of cytochromes P450 in tropical medicine. Curr Drug Targets 2006; 7: 1709–19.
[8] Maria, Giacomo et al. 2014. “Infection, Genetics and Evolution Absence of the Human CYP2C8 * 3 Allele in Ugandan Children Exposed to Plasmodium Falciparum Malaria.” Infection, Genetics and Evolution 27: 432–35. http://dx.doi.org/10.1016/j.meegid.2014.08.011.
[9] S. M. Mimche, C.-M. Lee, K. H. Liu, P. N. Mimche, R. D. Harvey, T. J. Murphy, B. A. Nyagode, D. P. Jones, T. J. Lamb and E. T. Morgan, "A non-lethal malarial infection results in reduced drug metabolizing enzyme expression and drug clearance in mice,"
[10] Totah RA, Rettie AE: Cytochrome P450 2 C8: substrates, inhibitors, pharmacogenetics, and clinical relevance. Clin Pharmacol Ther, Vol. 77 pp. 341-352, 2005.
[11] Klose TS, Blaisdell JA, Goldstein JA Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. Journal of Biochemical and Molecular Toxicology, Vol. 13, pp. 289–295, 1999.
[12] Cavaco I, Strömberg-Nörklit J, Kaneko A, Msellem MI, Dahoma M, Ribeiro VL, Bjorkman A, Gil JP: CYP2C8 polymorphism frequencies among malaria patients in Zanzibar. Eur J Clin Pharmacol, Vol. 61, pp. 15-18, 2005.
[13] Parikh S, Ouedraogo JB, Goldstein JA, Rosenthal PJ, Kroetz DL: Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther, Vol. 82, pp. 197-203, 2007.
[14] R. P. Gil and J. Pedro, "The pharmacogenetics of antimalaria artemisinin combination therapy," Expert Opinion on Drug Metabolism & Toxicology, pp. 1185-1200, 2011.
[15] J. A. G. Agúndez, "Editorial [Hot Topic: N-Acetyltransferases: Lessons Learned from Eighty Years of Research (Guest Editor: Jose A. G. Agundez)]," Current Drug Metabolism, vol. 9, no. 6, pp. 463-464, 2008.
[16] Antonio-Nkondjio, Christophe et al. 2019. “Review of Malaria Situation in Cameroon: Technical Viewpoint on Challenges and Prospects for Disease Elimination.” Parasites and Vectors 12 (1): 1–23. https://doi.org/10.1186/s13071-019-3753-8.
[17] C. V. Plowe, C. Roper, J. W. Barnwell, C. T. Happi, H. Joshi, W. F. Mbacham, S. R. Meshnick, K. Mugittu, I. Naidoo, R. N. Price, R. W. Shafer, C. H. Sibley, C. J. Sutherland, P. A. Zimmerman and P. Rosenthal, "World Antimalarial Resistance Network (WARN) III: Molecular markers for drug resistant malaria," Malaria Journal, vol. 6, no. 1, p. 121, 2007.
[18] Dai D, Zeldin DC, Blaisdell JA, Chanas B, Coulter SJ, Ghanayem BI, et al., "Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug pacilitaxel and arachidonic acid.," Pharmacogenetics, vol. 11, no. 7, pp. 75-79, 2001.
[19] Marwa, Karol J et al. 2014. “Cytochrome P450 Single Nucleotide Polymorphisms in an Indigenous Tanzanian Population : A Concern about the Metabolism of Artemisinin-Based Combinations.”: 1–7.
[20] Kudzi, William, Alexander N O Dodoo, and Jeremy J Mills. 2009. “In a Ghanaian Population.” 6: 8–13.
[21] Berzosa, Pedro et al. 2017. “Profile of Molecular Mutations in Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt Genes of Plasmodium Falciparum Related to Resistance to Different Anti- Malarial Drugs in the Bata District (Equatorial Guinea).” Malaria Journal: 1–10.
[22] Gupta, Himanshu et al. 2018. “Drug-Resistant Polymorphisms and Copy Numbers In.” 24 (1).
[23] Maraka, Moureen et al. 2020. “A Seven-Year Surveillance of Epidemiology of Malaria Reveals Travel and Gender Are the Key Drivers of Dispersion of Drug Resistant Genotypes in Kenya.” PeerJ: 1–27.
[24] Tinto, Halidou et al. 2008. “Chloroquine-Resistance Molecular Markers (Pfcrt T76 and Pfmdr-1 Y86) and Amodiaquine Resistance in Burkina Faso.” Tropical Medicine and International Health 13 (2): 238–40.
Cite This Article
  • APA Style

    Jean Paul Kengne Chedjou, Palmer Masumbe Netongo, Aristid Herve Mbange Ekollo, Cyrille Mbanwi Mbu’u, Lesley Ngum Ngum, et al. (2022). Relationship Between CYP2C8*2 and Pfmdr1 N86Y Polymorphisms in Patients with Uncomplicated Malaria in Yaounde, Centre Region of Cameroon. American Journal of Biomedical and Life Sciences, 10(3), 97-101. https://doi.org/10.11648/j.ajbls.20221003.16

    Copy | Download

    ACS Style

    Jean Paul Kengne Chedjou; Palmer Masumbe Netongo; Aristid Herve Mbange Ekollo; Cyrille Mbanwi Mbu’u; Lesley Ngum Ngum, et al. Relationship Between CYP2C8*2 and Pfmdr1 N86Y Polymorphisms in Patients with Uncomplicated Malaria in Yaounde, Centre Region of Cameroon. Am. J. Biomed. Life Sci. 2022, 10(3), 97-101. doi: 10.11648/j.ajbls.20221003.16

    Copy | Download

    AMA Style

    Jean Paul Kengne Chedjou, Palmer Masumbe Netongo, Aristid Herve Mbange Ekollo, Cyrille Mbanwi Mbu’u, Lesley Ngum Ngum, et al. Relationship Between CYP2C8*2 and Pfmdr1 N86Y Polymorphisms in Patients with Uncomplicated Malaria in Yaounde, Centre Region of Cameroon. Am J Biomed Life Sci. 2022;10(3):97-101. doi: 10.11648/j.ajbls.20221003.16

    Copy | Download

  • @article{10.11648/j.ajbls.20221003.16,
      author = {Jean Paul Kengne Chedjou and Palmer Masumbe Netongo and Aristid Herve Mbange Ekollo and Cyrille Mbanwi Mbu’u and Lesley Ngum Ngum and Calvino Tah Fomboh and Wilfred Fon Mbacham},
      title = {Relationship Between CYP2C8*2 and Pfmdr1 N86Y Polymorphisms in Patients with Uncomplicated Malaria in Yaounde, Centre Region of Cameroon},
      journal = {American Journal of Biomedical and Life Sciences},
      volume = {10},
      number = {3},
      pages = {97-101},
      doi = {10.11648/j.ajbls.20221003.16},
      url = {https://doi.org/10.11648/j.ajbls.20221003.16},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbls.20221003.16},
      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.},
     year = {2022}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Relationship Between CYP2C8*2 and Pfmdr1 N86Y Polymorphisms in Patients with Uncomplicated Malaria in Yaounde, Centre Region of Cameroon
    AU  - Jean Paul Kengne Chedjou
    AU  - Palmer Masumbe Netongo
    AU  - Aristid Herve Mbange Ekollo
    AU  - Cyrille Mbanwi Mbu’u
    AU  - Lesley Ngum Ngum
    AU  - Calvino Tah Fomboh
    AU  - Wilfred Fon Mbacham
    Y1  - 2022/06/30
    PY  - 2022
    N1  - https://doi.org/10.11648/j.ajbls.20221003.16
    DO  - 10.11648/j.ajbls.20221003.16
    T2  - American Journal of Biomedical and Life Sciences
    JF  - American Journal of Biomedical and Life Sciences
    JO  - American Journal of Biomedical and Life Sciences
    SP  - 97
    EP  - 101
    PB  - Science Publishing Group
    SN  - 2330-880X
    UR  - https://doi.org/10.11648/j.ajbls.20221003.16
    AB  - 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.
    VL  - 10
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • The Biotechnology Centre, University of Yaounde I, Yaounde, Cameroon

  • The Biotechnology Centre, University of Yaounde I, Yaounde, Cameroon

  • The Biotechnology Centre, University of Yaounde I, Yaounde, Cameroon

  • The Biotechnology Centre, University of Yaounde I, Yaounde, Cameroon

  • The Biotechnology Centre, University of Yaounde I, Yaounde, CameroonDepartment of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Yaounde, Cameroon

  • The Biotechnology Centre, University of Yaounde I, Yaounde, Cameroon

  • The Biotechnology Centre, University of Yaounde I, Yaounde, Cameroon

  • Sections