KCNJ11 gene E23K variant and therapeutic response to sulfonylureas

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• 作者：Martin Javorsky^a ; Lucia Klimcakova^b ; Zbynek Schroner^a ; Jozef Zidzik^b ; Eva Babjakova^a ; Maria Fabianova^a ; Miriam Kozarova^a ; Ruzena Tkacova^c ; Jan Salagovic^b ; Ivan Tkac^a ; ^{Ivan.Tkac@UPJS.sk}
• 关键词：Type 2 diabetes ; Pharmacogenetics ; Sulfonylurea ; KCNJ11 E23K variant
• 刊名：European Journal of Internal Medicine
• 出版年：2012
• 期刊代码：91_09536205
• 类别：med
• 出版时间：April, 2012
• 卷：23
• 期：3
• 页码：245-249
• 文件大小：175 K

摘要

Aims

Potassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive potassium (K_ATP) channel encoded by KCNJ11 gene is a therapeutical target for sulfonylureas. KCNJ11 E23K polymorphism was associated with type 2 diabetes in genetic association studies. The aim of the present pharmacogenetic study was to examine the effect of sulfonylurea treatment on glycemic control in relationship to KCNJ11 E23K variant.

Patients and methods

One hundred and one patients with type 2 diabetes who failed to achieve HbA1c < 7%on previous metformin monotherapy were included to the study. Sulfonylurea drug was given in addition to metformin. The main outcome of the study was reduction in HbA1c level (螖HbA1c) after 6-month sulfonylurea therapy. KCNJ11 genotypes were determined by real-time PCR with melting curve analysis.

Results

After 6-month treatment, KCNJ11 K-allele carriers had higher decrease in HbA1c compared with EE homozygotes in the dominant genetic model (1.04 卤 0.10 vs. 0.79 卤 0.12%, p = 0.036). In the log-additive model, greater mean reduction in HbA1c by 0.16%(95%CI 0.01-0.32, p = 0.038) per each K-allele was observed. The relationship of treatment response with KCNJ11 genotype was also significant in the biggest subgroup of patients treated with gliclazide (n = 55).

Conclusions

Carriers of the KCNJ11 K-allele have better therapeutic response to gliclazide. This observation might help to identify patients who will have the highest benefit from sulfonylurea treatment.