Single Nucleotide Polymorphisms Associated with Metformin and Sulphonylureas' Glycaemic Response among South African Adults with Type 2 Diabetes Mellitus.

Charity Masilela,Oladele Vincent Adeniyi,Brendon Pearce,Mongi Benjeddou,Joven Jebio Ongole

doi:10.3390/jpm11020104

Abstract

Aims: To examine the association of polymorphisms belonging to SLC22A1, SP1, PRPF31, NBEA, SCNN1B, CPA6 and CAPN10 genes with glycaemic response to metformin and sulphonylureas (SU) combination therapy among South African adults with diabetes mellitus type 2 (T2DM). Methods: A total of 128 individuals of Swati (n = 22) and Zulu (n = 106) origin attending chronic care for T2DM were recruited. Nine SNPs previously associated with metformin and SUs were selected and genotyped using MassArray. Uncontrolled T2DM was defined as HbA1c > 7%. The association between genotypes, alleles and glycaemic response to treatment was determined using multivariate logistic regression model analysis. Results: About 85.93% (n = 110) of the study participants were female and 77.34% (n = 99) had uncontrolled T2DM (HbA1c > 7%). In the multivariate (adjusted) logistic regression model analysis, the CC genotype of rs2162145 (CPA6), GG and GA genotypes of rs889299 (SCNN1B) were significantly associated with uncontrolled T2DM. On the other hand, the C allele of rs254271 (PRPF31) and the GA genotype of rs3792269 (CAPN10) were associated with controlled T2DM. A significant interaction between rs2162145 and rs889299 in response to metformin and SU combination therapy was observed. Conclusions: In this study, we reported the association of rs2162145 (CC) and rs889299 (GG and GA) with uncontrolled T2DM. We also reported the association of rs254271 (C) and rs3792269 (GA) with controlled T2DM in response to metformin and SU combination therapy. Furthermore, an interaction between rs2162145 and rs889299 was established, where the genotype combination GA (rs889299) and TT (rs2162145) was associated with uncontrolled T2DM.

Highlights

Diabetes mellitus (DM) is a chronic non-communicable disease that affects about463 million people worldwide [1]
The current study investigated the association of nine polymorphisms belonging to SLC22A1, Specificity protein 1 (SP1), pre-mRNA processing factor 31 (PRPF31), NBEA, SCNN1B, Carboxypeptidase A6 (CPA6) and Calpain 10 (CAPN10) genes with glycaemic response to metformin/SU
We investigated the effect of two SLC22A1 polymorphisms on glycaemic response to metformin/SU combination therapy in patients with type 2genotype diabetes combinations mellitus (T2DM)

Summary

Introduction

Diabetes mellitus (DM) is a chronic non-communicable disease that affects about463 million people worldwide [1]. According to the International Diabetes Federation (IDF), over 4.5 million South African adults were estimated to be living with DM in the year 2019. Using data from the South African National Health and Nutrition Survey (2011–2012), Stokes et al showed that 18.1% of South Africans were treated but exhibited poor glycaemic control (HbA1C > 7%) [2]. Uncontrolled DM and its complications have a huge and rapidly growing impact on the South African health care system [1,2,3]. Improving glycaemic control in individuals diagnosed with DM and initiated on treatment will require concerted efforts from many fronts including individual behavioural changes, public health efforts and tailored medical care that is guided by pharmacogenomics strategies

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