Association of SLC2A2 rs8192675 and SLC22A1 rs72552763 polymorphisms to metformin treatment outcomes in Ethiopian patients with type 2 diabetes mellitus
| dc.contributor.advisor | Shibeshi,Workineh (PhD) | |
| dc.contributor.advisor | Engidawork,Ephrem(PhD) | |
| dc.contributor.advisor | Huri, Hasniza Zaman(PhD) | |
| dc.contributor.advisor | Sirgu,Sisay(MD) | |
| dc.contributor.author | Abdi,Abraham Degaga | |
| dc.date.accessioned | 2025-08-12T19:37:22Z | |
| dc.date.available | 2025-08-12T19:37:22Z | |
| dc.date.issued | 2024-04 | |
| dc.description.abstract | Metformin is recommended as the first-line oral glucose-lowering agent by most clinical guidelines for people with type 2 diabetes mellitus (T2DM), although there are extensive variations in the metformin treatment outcomes, related to the differences in individual genetic profiles. Thus, in this study the association of SLC2A2 rs8192675 and SLC22A1 rs72552763 polymorphisms with metformin treatment response and SLC22A1 rs72552763 with metformin gastrointestinal intolerance were investigated in Ethiopian patients with T2DM. Recently diagnosed patients with T2DM were enrolled at St Paul’s Hospital Millennium Medical College. In the metformin treatment response study, a prospective observational cohort was conducted on 86 patients receiving metformin treatment for < 1 year. The participants were classified into metformin responders and non-responders based on a cut-off value of 0.5% reduction in HbA1c levels. Genotyping of rs8192675 and rs72552763 was performed using TaqMan® Pre-Designed and Drug Metabolism Enzyme SNP Genotyping Assay, respectively. The association of each one of the polymorphisms with metformin response was assessed by measuring the change in HbA1c levels, while the association of rs8192675 polymorphism with metformin response in diabetic dyslipidemia was assessed by measuring the absolute change in lipid parameters as well as HbA1c levels. On the other hand, in the metformin gastrointestinal intolerance study, a retrospective study was conducted in 47 patients on metformin treatment for < 3 years. The association of rs72552763 polymorphism to metformin-induced gastrointestinal intolerance was assessed based on switching to a new class of glucose-lowering agents or failure to up-titrate metformin dose due to gastrointestinal intolerance. Dyslipidemia was defined in accordance with the adult treatment panel III. Chi-square, logistic regression, student’s t-test, Mann-Whitney and Kruskal-Wallis statistical tests were used as applicable. A p-value of less than 0.05 was taken as statistically significant. The minor allele frequency iv (MAF) of the C-allele in the T>C substitution SNP of SLC2A2 (rs8192675) was 66.2% while the MAF of the 3-base pair (GAT) deletion mutation at rs72552763 was 9.4% in our study population. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to wild-type GAT_GAT (G_G) genotypes 3.675 95% CI (1.005– 13.436) (p = 0.049). Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes 7% vs 8% (p=0.015). However, the association of rs72552763 with metformin response was not replicated at the allele level. Furthermore, the minor del_allele was significantly associated with good glycemic control compared to the G_allele 3.206 95% CI (1.165–8.823) (p = 0.016), though not replicated at del_G genotypes level. In contrast, the rs8192675 polymorphism showed no significant association with metformin treatment response, glycemic control and dyslipidemia. Likewise, no significant association was also observed between rs72552763 and metformin- induced gastrointestinal intolerance. The prevalence of dyslipidemia was 92.1 %. The prevalence of mixed atherogenic dyslipidemia, combined dyslipidemia and isolated dyslipidemia was 37 (29.1 %), 34 (26.8 %), and 27 (21.3%), respectively. The findings demonstrated that heterozygous carriers of the Met420del variants of SLC22A1 have an increased response to metformin. However, rs8192675 and rs72552763 genetic polymorphisms were not associated with metformin treatment response and metformin- induced gastrointestinal intolerance, respectively. The study also indicated a high prevalence of dyslipidemia in people with T2DM, with atherogenic mixed dyslipidemia being the commonest pattern. | |
| dc.identifier.uri | https://etd.aau.edu.et/handle/123456789/6437 | |
| dc.language.iso | en_US | |
| dc.publisher | Addis Ababa University | |
| dc.subject | Type 2 diabetes mellitus | |
| dc.subject | Metformin Response | |
| dc.subject | SLC2A2 | |
| dc.subject | rs8192675 | |
| dc.subject | diabetic dyslipidemia | |
| dc.subject | Metformin intolerance | |
| dc.subject | SLC22A1 | |
| dc.subject | rs72552763 | |
| dc.subject | Ethiopia | |
| dc.title | Association of SLC2A2 rs8192675 and SLC22A1 rs72552763 polymorphisms to metformin treatment outcomes in Ethiopian patients with type 2 diabetes mellitus | |
| dc.type | Thesis |