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CYP2C9, KCNJ11 and ABCC8 polymorphisms and the response to sulphonylurea treatment in type 2 diabetes patients

  • Pharmacogenetics
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Abstract

Purpose

Sulphonylureas (SU) are widely used in the management of type 2 diabetes. We investigated the influence of CYP2C9, KCNJ11 and ABCC8 polymorphisms on the response to SU currently used in everyday clinical practice.

Methods

Patients treated for type 2 diabetes with sulphonylurea in monotherapy (n = 21) or in combination with metformin (n = 135) were provided with glucose-monitoring devices and instructed to measure fasting blood glucose levels once per week and additionally at any signs and symptoms suggesting low blood glucose for a period of three months. All patients were genotyped for CYP2C9 rs1799853 and rs1057910 (*2 and *3 allele, respectively), KCNJ11 rs5219 and rs5215, and ABCC8 rs757110.

Results

The average duration of diabetes in the study group was 10.6 ± 7.1 years. Most of the patients achieved relatively good blood glucose control (HbA1c 7.0 ± 0.9). In total, 76 hypoglycemia events were observed (mean 0.48 ± 1.3). No severe hypoglycemia was reported; the lowest blood glucose was 2.1 mmol/l. Although 124 (79.5 %) patients never experienced hypoglycemia, 32 (20.5 %) patients experienced from one to eight events. None of the investigated polymorphisms influenced HbA1c levels or risk for hypoglycemia episodes in the whole group of patients. CYP2C9 genotype significantly influenced the occurrence of hypoglycemia events among the elderly patients (aged 60 years and over; n = 103). Among them, carriers of two wild-type alleles suffered 0.36 ± 0.98 events, while patients with one or two polymorphic alleles had 0.79 ± 1.7 or 2.67 ± 4.6 events, respectively (p = 0.014).

Conclusions

Our results indicate that the CYP2C9 genotype may influence the risk for hypoglycemia events in elderly patients, but not in the overall population of type 2 diabetes patients.

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Acknowledgments

We wish to acknowledge the clinical nurse Mrs. Kirič Nevenka for her support with the clinical part of the study, Mrs. Savica Soldat BSc for her expert technical assistance and Miss Katja Goricar BSc for her support with the statistical analysis.

The study was financially supported by the Ministry of Education, Science, and Sport of the Republic of Slovenia (Grants Nos P1-0170 and P3-0298).

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. General Hospital Trbovlje, Trbovlje, Slovenia

    Jasna Klen

  2. Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Vita Dolžan

  3. Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Zaloška c. 7, 1000, Ljubljana, Slovenia

    Andrej Janež

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  1. Jasna Klen
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Correspondence to Andrej Janež.

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Klen, J., Dolžan, V. & Janež, A. CYP2C9, KCNJ11 and ABCC8 polymorphisms and the response to sulphonylurea treatment in type 2 diabetes patients. Eur J Clin Pharmacol 70, 421–428 (2014). https://doi.org/10.1007/s00228-014-1641-x

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