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

J Pers Med. 2021 Feb 6;11(2):104. doi: 10.3390/jpm11020104.


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.

Keywords: combination therapy; metformin; single nucleotide polymorphisms; sulphonylureas; type 2 diabetes.