乌克兰的成年发病型糖尿病：基因、临床表型与治疗

MODY in Ukraine: genes, clinical phenotypes and treatment.

作者信息

Globa Evgenia, Zelinska Nataliya, Elblova Lenka, Dusatkova Petra, Cinek Ondrej, Lebl Jan, Colclough Kevin, Ellard Sian, Pruhova Stepanka

机构信息

出版信息

J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1095-1103. doi: 10.1515/jpem-2017-0075.

DOI:10.1515/jpem-2017-0075

PMID:28862987

Abstract

BACKGROUND

Maturity-onset diabetes of the young (MODY) has not been previously studied in Ukraine. We investigated the genetic etiology in a selected cohort of patients with diabetes diagnosed before 18 years of age, and in their family members.

METHODS

Genetic testing of the most prevalent MODY genes (GCK, HNF1A, HNF4A, HNF1B and INS) was undertaken for 36 families (39 affected individuals) by Sanger or targeted next generation sequencing.

RESULTS

A genetic diagnosis of MODY was made in 15/39 affected individuals from 12/36 families (33%). HNF1A and HNF4A MODY were the most common subtypes, accounting for 9/15 of MODY cases. Eight patients with HNF1A or HNF4A MODY and inadequate glycemic control were successfully transferred to sulfonylureas. Median HbA1c decreased from 67 mmol/mol (range 58-69) to 47 mmol/mol (range 43-50) (8.3% [7.5-8.5] to 6.4% [6.1-6.7]) 3 months after transfer (p=0.006).

CONCLUSIONS

Genetic testing identified pathogenic HNF1A and HNF4A variants as the most common cause of MODY in Ukraine. Transfer to sulfonylureas substantially improved the glycemic control of these patients.

摘要

背景

乌克兰此前尚未对青年发病的成年型糖尿病（MODY）进行过研究。我们对一组18岁之前被诊断为糖尿病的患者及其家庭成员的遗传病因进行了调查。

方法

通过桑格测序法或靶向二代测序技术，对36个家庭（39名患者）的最常见MODY基因（GCK、HNF1A、HNF4A、HNF1B和INS）进行了基因检测。

结果

在36个家庭中的12个家庭（33%）的39名患者中，有15名做出了MODY的基因诊断。HNF1A和HNF4A MODY是最常见的亚型，占MODY病例的9/15。8名HNF1A或HNF4A MODY且血糖控制不佳的患者成功改用了磺脲类药物。改用药物3个月后，糖化血红蛋白（HbA1c）中位数从67 mmol/mol（范围58 - 69）降至47 mmol/mol（范围43 - 50）（8.3% [7.5 - 8.5]降至6.4% [6.1 - 6.7]）（p = 0.006）。