Evaluation of the Suitability of 19 Pharmacogenomics Biomarkers for Individualized Metformin Therapy for Type 2 Diabetes Patients

Lettilia Xhakaza 1, Zainonesa Abrahams-October 1, Brendon Pearce 1, Charity Mandisa Masilela 1, Oladele Vincent Adeniyi 2, Rabia Johnson 3 4, Joven Jebio Ongole 5, Mongi Benjeddou 1

Affiliations

PMID: 32609649
DOI: 10.1515/dmdi-2020-0111

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.

Keywords: HbA1c; Nguni population; genetic polymorphisms; metformin; type 2 diabetes.