Pharmacogenetics of Pain Management in Zimbabwean Patients With Sickle Cell Disease

Abstract

Background: Pain is a common cause of hospitalization in sickle cell disease (SCD) patients. Failure to effectively control pain remains a challenge in patient care. Materials & methods: The authors conducted a cross-sectional study to determine the effect of CYP2D6 and UGT2B7 polymorphisms on pain management in 106 Zimbabwean SCD patients. Participant information was collected on a questionnaire. Genotyping was conducted using the GenoPharm^® pharmacogenomics open array panel containing CYP2D6 and UGT genetic variants implicated in opioid response. Results: The reduced function alleles CYP2D6*17 and *29 had high frequencies of 15.9% and 12.9%, respectively. UGT2B7 rs73823859 showed a statistically significant correlation with pain levels (p = 0.0454). Conclusion: This study demonstrated the role of UGT2B7 polymorphism in SCD patient pain management.

Tweetable abstract

Failure to effectively control pain remains a challenge in sickle cell disease (SCD) patients. This cross-sectional study in 106 Zimbabwean SCD patients demonstrated the role of UGT2B7 polymorphism in SCD patient pain management. #AiBST #pharmacogenetics #sickle cell disease

Keywords::

• codeine
• CYP2D6
• genetic variation
• morphine
• opioids
• pharmacogenomics
• tramadol
• UGT2B7

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/pgs-2023-0045

Author contributions

Conceptualization and methodology: C Masimirembwa and P Kuona; formal analysis: NL Mapira and RS Thelingwani; investigation: NL Mapira, P Kuona and C Masimirembwa; resources and funding acquisition: C Masimirembwa; data curation: NL Mapira and Z Chikwambi; original draft preparation: NL Mapira and RS Thelingwani; review and editing: P Kuona, Z Chikwambi and C Masimirembwa; supervision: RS Thelingwani, Z Chikwambi and P Kuona; project administration: Z Chikwambi; all authors have read and agreed to the published version of the manuscript.

Acknowledgments

The authors would like to acknowledge all the study participants and their families, the study team, the staff at Parirenyatwa Group of Hospitals in Harare Zimbabwe and the Sickle Haemoglobinopathy Research in Zimbabwe (SHAZ) sickle cell registry, Pageneck Chikondowa and Tinashe Mazhindu for being actively involved in the recruitment of SCD participants, Comfort Kanji for assistance with the genotyping assays and the staff at the African Institute of Biomedical Science and Technology (AiBST). They would also like to acknowledge the Consortium for Genomics and Therapeutics in Africa: Collen Masimirembwa – Zimbabwe, Collet Dandara – South Africa, Oluseye Bolaji – Nigeria, Bernards Ogutu – Kenya, Ntokozo Ndlovu – Zimbabwe, Margaret Borok – Zimbabwe, Patience Kuona – Zimbabwe and Jonathan Matenga – Zimbabwe.

Financial & competing interests disclosure

This research was funded by a European & Developing Countries Clinical Trials Partnership (EDCTP) grant (TMA2016SF-1508), Bill and Melinda Gates Foundation (BGMF) grant investment ID INV-036801 and National Institutes of Health (NIH) grant number 5P20CA210677. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. The study was approved by the University of Zimbabwe College of Health Sciences, Joint Research Ethics Committee (JREC; ref. 225/22) and the Medical Research Council of Zimbabwe (MRCZ; ref. MRCZ/B/2307).

Data sharing statement

Data are contained within this article or supplementary material. Additional data that support the findings of this study are available on request from the corresponding author. The data are not publicly available because of privacy and ethical restrictions.

Additional information

Funding

This research was funded by a European & Developing Countries Clinical Trials Partnership (EDCTP) grant (TMA2016SF-1508), Bill and Melinda Gates Foundation (BGMF) grant investment ID INV-036801 and National Institutes of Health (NIH) grant number 5P20CA210677. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.