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A pharmacogenetic pilot study of CYP2C9 common genetic variant and sulfonylureas therapeutic response in type 2 diabetes mellitus patients

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Abstract

Background

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is associated with elevated blood glucose levels. Sulfonylureas (SFUs) are the most widely used among the oral antidiabetic drugs that are highly metabolized by cytochrome P450 family 2 subfamily C member 9 (CYP2C9). The CYP2C9 has been shown to be associated with a better glycemic response to SFUs and a lower treatment failure rate. The aim of the present study was to assess the influence of the CYP2C9 rs1067910 gene variant on the SFUs response in a group of Iranian patients for the first time.

Methods

Blood samples were taken from 30 patients with T2DM under sulfonylurea treatment. DNA extraction was performed using Salting out method, and then genotyping was performed by polymerase chain reaction (PCR) followed by Sanger sequencing.

Results

There was no significant difference in the fasting blood sugar (FBS) between T2DM patients with different genotypes before and after the treatment with SFUs (P = 0.073 and P = 0.893, respectively). Although HbA1c was significantly different among AA, CA and CC carriers before (P = 0.001) and after (P = 0.018) treatment, no significant change was observed after treatment in all three groups.

Conclusions

In the present study based on only 30 samples in pilot survey, it is shown that the therapeutic response to SFUs was not related to rs1057910 CYP2C9 variant.

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Data availability

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

Abbreviations

T2DM:

Type 2 diabetes mellitus

SNP:

Single nucleotide polymorphisms

SFUs:

Sulfonylureas

HbA1c:

Hemoglobin A1C

CYP2C9:

Cytochrome P450 family 2 subfamily C member 9

ADA:

American Diabetes Association

PCR:

Polymerase chain reaction

FBS:

Fasting blood sugar

BMI:

Body mass index

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Acknowledgements

The authors would like to give special thanks to the T2DM patients participating in this study.

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Authors

Contributions

MH managed the project and provided guidance to the research; ED and NS drafted the manuscript and performed lab genotyping; MA performed the statistical analysis; HRAM: provided clinical guidance to the research. All authors contributed to and approved the final version of the manuscript.

Corresponding author

Correspondence to Mandana Hasanzad.

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Consent for publication

All patients signed written consent forms and the study was approved by the ethical committee (Ethic Code: IR.IAU.PS.REC.1399.044).

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The authors have no conflict of interest to report.

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Didari, E., Sarhangi, N., Afshari, M. et al. A pharmacogenetic pilot study of CYP2C9 common genetic variant and sulfonylureas therapeutic response in type 2 diabetes mellitus patients. J Diabetes Metab Disord 20, 1513–1519 (2021). https://doi.org/10.1007/s40200-021-00894-0

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