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Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian Gong, Hong Lian, Yating Li, Xiaoling Cai, Wei Liu, Yingying Luo, Meng Li, Si-min Zhang, Rui Zhang, Lingli Zhou, Yu Zhu, Qian Ren, Xiuying Zhang, Jing Chen, Jing Wu, Xianghai Zhou, Xirui Wang, Xueyao Han, Linong Ji
Received March 20, 2024  Accepted July 24, 2024  Published online November 13, 2024  
DOI: https://doi.org/10.4093/dmj.2024.0159    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
Reviews
Challenges in Diagnosing Type 1 Diabetes in Different Populations
Marian Rewers
Diabetes Metab J. 2012;36(2):90-97.   Published online April 17, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.2.90
  • 4,864 View
  • 52 Download
  • 33 Crossref
AbstractAbstract PDFPubReader   

Diabetes affects today an estimated 366 million people world-wide, including 20 million to 40 million of patients with type 1 diabetes (T1D). While T1D accounts for 5% to 20% of those with diabetes, it is associated with higher morbidity, mortality and health care cost than the more prevalent type 2 diabetes. Patients with T1D require exogenous insulin for survival and should be identified as soon as possible after diagnosis to avoid high morbidity due to a delay in insulin treatment. It is also important to present to the patient correct prognosis that differs by the type of diabetes. From the research point of view, correct classification should help to identify the etiologies and to develop specific prevention for T1D. This review summarizes evidence that may be helpful in diagnosing T1D in various ethnic groups. Challenges in interpretation of results commonly used to determine the type of diabetes are highlighted.

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The Importance of Global Studies of the Genetics of Type 2 Diabetes
Mark I. McCarthy
Diabetes Metab J. 2011;35(2):91-100.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.91
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  • 31 Download
  • 12 Crossref
AbstractAbstract PDFPubReader   

Genome wide association analyses have revealed large numbers of common variants influencing predisposition to type 2 diabetes and related phenotypes. These studies have predominantly featured European populations, but are now being extended to samples from a wider range of ethnic groups. The transethnic analysis of association data is already providing insights into the genetic, molecular and biological causes of diabetes, and the relevance of such studies will increase as human discovery genetics increasingly moves towards sequencing-based approaches and a focus on low frequency and rare variants.

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The Epidemiology of Diabetes in Korea: From the Economics to Genetics
Nam H. Cho
Korean Diabetes J. 2010;34(1):10-15.   Published online February 28, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.1.10
  • 3,354 View
  • 54 Download
  • 17 Crossref
AbstractAbstract PDFPubReader   

To determine the factors responsible for the dramatic increase in the prevalence of diabetes in Korea. A computerized literature survey was conducted to evaluate the risk factors for Type 2 diabetes mellitus (T2DM) in Korea, including genome-wide association studies. National Statistics gross national income data was integrated with the reported prevalence of diabetes to evaluate the relationship between diabetes and the economic growth. The strength of the association was evaluated using measures of effect size, such as odds ratio and relative risks. The putative risk factors identified in Korean studies are very similar to the risk factors identified from the other countries, including genetic background. Genome-wide association studies reported relative risks of 1.5 or less, indicating that no single gene is associated with the risk of T2DM. The scientific evidence suggests that the dramatic increase in the incidence and prevalence of T2DM in Korea is related to the economic development of Korea, which has a direct influence on health policy, as well as an individual's health behaviors. We expect to observe the current diabetes incidence rates until the key risk factors are present for long enough in our society, at which point we would expect to start observing a more gradual increase in both the incidence and prevalence of T2DM in Korea.

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