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Association of ABCC8 gene variants with response to sulfonylurea in type 2 diabetes mellitus

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Abstract

Background

Diabetes mellitus (DM) is associated with high blood glucose levels and sulfonylureas (SFUs) are one of the treatment options for DM. SFUs bind to sulfonylurea-1 receptor (SUR1), which is encoded by the ABCC8 gene and leads to blood glucose reduction. Genetic variants like rs757110 and rs1799854 of ABCC8 can influence the response to the drug’s efficiency. Therefore, this study aimed to investigate the association between the ABCC8 rs757110 and rs1799854 genetic variants and response to SFUs treatment.

Methods

Totally, 61 DM patients with SFUs treatment were included. Baseline characteristics of the patients were recorded and 5 ml of blood was taken from each patient. After DNA extraction, a sequence containing rs757110 and rs1799854 was synthesized by the PCR method, and the PCR products were used for Sanger sequencing.

Results

Frequencies of GG, GA, and AA genotypes of rs1799854 variant was 12 (40%), 14 (46.7%), and 4 (13.3%), and the frequencies of CC, AC, and AA genotypes for rs757110 variant was 3 (9.7%), 5 (16.1%) and 23 (74.2%) in, respectively. Patients with different genotypes had the same age, BMI (body mass index), initial FBS (Fasting blood sugar), initial HbA1c, treatment duration, gender and history of smoking, alcohol consumption, and exercise. There was no significant difference in FBS and HbA1c changes after SFUs treatment between patients with rs757110 variant (p = 0.39 for FBS and p = 0.76 for HbA1c) and rs1799854 (p = 0.24 for FBS and p = 0.36 for HbA1c).

Conclusion

The rs1799854 and rs757110 variants of the ABCC8 gene had no significant influence on response to SFUs treatment.

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Data availability

This project’s data will be open to the public.

Abbreviations

DM:

diabetes mellitus

SFUs:

Sulfonylureas

SUR1:

sulfonylurea-1 receptor

PCR:

polymerase chain reaction

BMI:

body mass index

FBS:

fasting blood sugar

HbA1c:

Hemoglobin A1c

T1D:

type 2 diabetes

T2D:

type 2 diabetes

GDM:

gestational diabetes

T1DM:

In type 1 diabetes mellitus

T2DM:

type 2 diabetes mellitus

SD:

standard deviation

EDTA:

ethylenediamine tetraacetic acid

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Acknowledgements

The authors thank to T2DM patients who participated in this study.

Funding

No funding was obtained.

Author information

Authors and Affiliations

  1. Medical Genomics Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Melika Azimi & Melika Paseban

  2. Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Sahar Ghareh

  3. Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Farshad Sharifi

  4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Farshad Sharifi

  5. Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Fatemeh Bandarian

  6. Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mandana Hasanzad

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  1. Melika Azimi
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Contributions

MA and MP drafted the manuscript and performed lab genotyping; SGH provided clinical guidance to the research; FSH performed the statistical analysis; FB managed the project; MH provided genetic guidance to the research. All authors contributed to and approved the final version of the manuscript.

Corresponding authors

Correspondence to Fatemeh Bandarian or Mandana Hasanzad.

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Competing of interest

There are no conflicts of interest declared by the authors.

Consent for publication

The present study research is approved by the ethics committee of Islamic Azad University and all T2DM patients signed written consent forms.

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Melika Azimi and Melika Paseban both authors contribute the first authorship.

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Azimi, M., Paseban, M., Ghareh, S. et al. Association of ABCC8 gene variants with response to sulfonylurea in type 2 diabetes mellitus. J Diabetes Metab Disord 22, 649–655 (2023). https://doi.org/10.1007/s40200-023-01189-2

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  • DOI: https://doi.org/10.1007/s40200-023-01189-2

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