<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated blood glucose levels and is influenced by both genetic and environmental factors. It is treated with various classes of oral antidiabetic drugs, however, response to treatment is highly variable with patients failing to achieve adequate glycemic control. Treatment response variability has been associated with single nucleotide polymorphisms (SNPs) which influence the pharma-cokinetics and pharmacodynamics of drug(s). The aim of this study was to evaluate the genetic association of 17 SNPs and the response to metformin therapy in patients diagnosed with diabetes from the indigenous Nguni population of South Africa. One hundred and forty indigenous African patients diagnosed with T2DM were recruited and genotyped using the MassARRAY® system. Therapeutic response of patients was ascertained by a change in Hb A<sup>1c</sup>. Two SNPs (rs1801282 and rs6265) were monomorphic. All other variants were within the Hardy-Weinberg equilibrium (HWE). The T allele of the <italic>SLC</italic> variant rs316009 [odds ratio (OR) = 0.25, 95% confidence interval (95% CI) = 0.01-0.09, <italic>p</italic> value = 0.044] and the CT genotype of the <italic>PCK1</italic> variant rs4810083 (OR = 2.80, 95% CI = 1.01-7.79, <italic>p</italic> value = 0.049) were associated with an improved response to treatment after adjustment. No association was observed with post Bonferroni correction. Moreover, this study provides important additional data regarding possible associations between genetic variants and metformin therapy outcomes. In addition, this is one of the first studies providing genetic data from the understudied indigenous sub-Saharan African populations.</p></abstract>

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated blood glucose levels and is influenced by both genetic and environmental factors. It is treated with various classes of oral antidiabetic drugs, however, response to treatment is highly variable with patients failing to achieve adequate glycemic control. Treatment response variability has been associated with single nucleotide polymorphisms (SNPs) which influence the pharma-cokinetics and pharmacodynamics of drug(s). The aim of this study was to evaluate the genetic association of 17 SNPs and the response to metformin therapy in patients diagnosed with diabetes from the indigenous Nguni population of South Africa. One hundred and forty indigenous African patients diagnosed with T2DM were recruited and genotyped using the MassARRAY® system. Therapeutic response of patients was ascertained by a change in Hb A1c. Two SNPs (rs1801282 and rs6265) were monomorphic. All other variants were within the Hardy-Weinberg equilibrium (HWE). The T allele of the SLC variant rs316009 [odds ratio (OR) = 0.25, 95% confidence interval (95% CI) = 0.01-0.09, p value = 0.044] and the CT genotype of the PCK1 variant rs4810083 (OR = 2.80, 95% CI = 1.01-7.79, p value = 0.049) were associated with an improved response to treatment after adjustment. No association was observed with post Bonferroni correction. Moreover, this study provides important additional data regarding possible associations between genetic variants and metformin therapy outcomes. In addition, this is one of the first studies providing genetic data from the understudied indigenous sub-Saharan African populations.

Genetic association of solute carrier transporter gene variants with metformin response

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated blood glucose levels and is influenced by both genetic and environmental...

Genetic association of solute carrier transporter gene variants with metformin response

Article Category: Original Article

Data publikacji: 27 lip 2021

Zakres stron: 47 - 56

DOI: https://doi.org/10.2478/bjmg-2021-0004

Słowa kluczowe
Single nucleotide polymorphisms (SNPs), variants, South African cohort, Treatment response, Type 2 diabetes mellitus (T2DM)

© 2021 Abrahams-October Z, Xhakaza L, Pearce B, Mandisa Masilela C, Benjeddou M, Vincent Adeniyi O, Johnson R, Jebio Ongole J, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Genetic association of solute carrier transporter gene variants with metformin response

Article Category: Original Article

Data publikacji: 27 lip 2021

Zakres stron: 47 - 56

DOI: https://doi.org/10.2478/bjmg-2021-0004

Słowa kluczoweSingle nucleotide polymorphisms (SNPs), variants, South African cohort, Treatment response, Type 2 diabetes mellitus (T2DM)

© 2021 Abrahams-October Z, Xhakaza L, Pearce B, Mandisa Masilela C, Benjeddou M, Vincent Adeniyi O, Johnson R, Jebio Ongole J, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Słowa kluczowe
Single nucleotide polymorphisms (SNPs), variants, South African cohort, Treatment response, Type 2 diabetes mellitus (T2DM)