Abstract
Objectives
Type 2 Diabetes mellitus is a progressive metabolic disease characterized by relative insulin insufficiency and insulin resistance resulting in hyperglycemia. Despite the widespread use of metformin, there is considerable variation in treatment response; with approximately one-third of patients failing to achieve adequate glycemic control. Studies have reported the involvement of single nucleotide polymorphisms and their interactions in genetic pathways i.e., pharmacodynamics and pharmacokinetics. This study aims to investigate the association between 19 pharmacogenetics biomarkers and response to metformin treatment.
Methods
MassARRAY panels were designed and optimized by Inqaba Biotechnical Industries, to genotype 19 biomarkers for 140 type 2 diabetic outpatients.
Results
The CT genotype of the rs12752688 polymorphism was significantly associated with increased response to metformin therapy after correction (OR=0.33, 95% CI [0.16–0.68], p-value=0.006). An association was also found between the GA genotype of SLC47A2 rs12943590 and a decreased response to metformin therapy after correction (OR=2.29, 95% CI [1.01–5.21], p-value=0.01).
Conclusions
This is the first study investigating the association between genetic variants and responsiveness to medication for diabetic patients from the indigenous Nguni population in South Africa. It is suggested that rs12752688 and rs12943590 be included in pharmacogenomics profiling systems to individualize metformin therapy for diabetic patients from African populations.
Acknowledgments
The authors would also like to thank the study participants, Cecilia Makiwane Hospital and the Department of Health Eastern Cape.
Research funding: The work reported herein was made possible through funding by the South African Medical Research Council through its Division of Research Capacity Development under funding received from the South African National Treasury. The content here of is the sole responsibility of the authors and do not necessarily represent the official views of the SAMRC or the funders. In addition, partial funding from the National Research Foundation of South African and the University of the Western Cape was used for this study.
Author contributions: LX conducted investigation, sample collection, data curation, formal data analysis, writing original draft, and editing of subsequent drafts. ZA provided methodology development, formal data analysis, and review and editing of drafts. BP provided methodology development, data curation, formal data analysis, and writing and editing of drafts. CM provided investigation, formal data analysis, and review and writing of drafts. OA provided investigation sites, resources, and data curation. RJ conducted methodology development and provided resources and methodology criteria. JO provided investigation sites, resources and methodology criteria. MB conceived the study, provided resources and data curation. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest. The authors declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Ethical clearance for this study was obtained from the Senate Research Committee of the University of the Western Cape (Ethics clearance number BM/16/5/19).
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