TCF7L2 rs7903146 C>T gene polymorphism is not associated with hypoglycemia in sulfonylurea-treated type 2 diabetic patients

Georgia Ragia; Evgenia Katsika; Charalampia Ioannou; Vangelis G Manolopoulos

doi:10.1515/dmdi-2020-0168

TCF7L2 rs7903146 C>T gene polymorphism is not associated with hypoglycemia in sulfonylurea-treated type 2 diabetic patients

Drug Metab Pers Ther. 2020 Dec 24. doi: 10.1515/dmdi-2020-0168. Online ahead of print.

Authors

Georgia Ragia¹, Evgenia Katsika¹, Charalampia Ioannou¹, Vangelis G Manolopoulos^{1

2}

Affiliations

¹ Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
² Clinical Pharmacology and Pharmacogenetics Unit, Academic General Hospital of Alexandroupolis, Alexandroupolis, Greece.

PMID: 33780196
DOI: 10.1515/dmdi-2020-0168

Abstract

Objectives: Hypoglycemia is the most common adverse effect of sulfonylureas (SUs) and a major concern when using these drugs. Transcription factor 7-like 2 (TCF7L2) rs7903146 C>T polymorphism is an established and well characterized genetic marker of type 2 diabetes (T2DM) risk. The aim of the present study was to analyze the potential association of TCF7L2 rs7903146 C>T polymorphism with SU-induced hypoglycemia in a well characterized cohort of SU-treated patients previously genotyped for cytochrome P450 2C9 (CYP2C9) and P450 oxidoreductase (POR).

Methods: The study group consisted of 176 SU-treated T2DM patients of whom 92 had experienced at least one drug-associated hypoglycemic event. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for TCF7L2 rs7903146 genotyping.

Results: TCF7L2 rs7903146 C>T genotype and allele frequency did not differ between cases and controls (p=0.745 and 0.671, respectively). In logistic regression analysis adjusted for other factors affecting hypoglycemia, including CYP2C9 and POR genotypes, TCF7L2 rs7903146 C>T polymorphism did not increase the risk of hypoglycemia (OR=1.238, 95% C.I.=0.750-2.044, p=0.405).

Conclusions: TCF7L2 rs7903146 C>T polymorphism is not associated with SU-induced hypoglycemia. Identifying additional gene polymorphisms associated with SU-induced hypoglycemia is crucial for improving T2DM patient therapy with SUs.

Keywords: CYP2C9; POR; TCF7L2; hypoglycemia; sulfonylurea pharmacogenomics.