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Genetics/Genomes/Proteomics/Metabolomics

Low-Frequency Genetic Variant in the Hepatic Glucokinase Gene Is Associated With Type 2 Diabetes and Insulin Resistance in Chinese Population

  1. Yumin Ma1,
  2. Yingying Luo1,
  3. Siqian Gong1,
  4. Xianghai Zhou1,
  5. Yufeng Li2,
  6. Wei Liu1,
  7. Simin Zhang1,
  8. Xiaoling Cai1,
  9. Qian Ren1,
  10. Lingli Zhou1,
  11. Xiuying Zhang1,
  12. Yanai Wang1,
  13. Xiuting Huang1,
  14. Xueying Gao1,
  15. Mengdie Hu1,
  16. Xueyao Han1⇑ and
  17. Linong Ji1⇑
  1. 1Departments of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, China
  2. 2Departments of Endocrinology and Metabolism, Beijing Pinggu Hospital, Beijing, China
  1. Corresponding author: Linong Ji, jiln{at}bjmu.edu.cn, or Xueyao Han, xueyaohan{at}sina.com
  1. Y.M., Y.Lu., and S.G. equally contributed to this work.

Diabetes 2021 Mar; 70(3): 809-816. https://doi.org/10.2337/db20-0564
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Abstract

Glucokinase (GCK) regulates insulin secretion and hepatic glucose metabolism, and its inactivating variants could cause diabetes. We aimed to evaluate the association of a low-frequency variant of GCK (rs13306393) with type 2 diabetes (T2D), prediabetes, or both (impaired glucose regulation [IGR]) in a Chinese population. An association study was first conducted in a random cluster sampling population (sample 1: 537 T2D, 768 prediabetes, and 1,912 control), and then another independent population (sample 2: 3,896 T2D, 2,301 prediabetes, and 868 control) was used to confirm the findings in sample 1. The A allele of rs13306393 was associated with T2D (odds ratio 3.08 [95% CI 1.77–5.36], P = 0.00007) in sample 1; rs13306393 was also associated with prediabetes (1.67 [1.05–2.65], P = 0.03) in sample 2. In a pooled analysis of the two samples, the A allele increased the risk of T2D (1.57 [1.15–2.15], P = 0.005), prediabetes (1.83 [1.33–2.54], P = 0.0003) or IGR (1.68 [1.26–2.25], P = 0.0004), insulin resistance estimated by HOMA (β = 0.043, P = 0.001), HbA1c (β = 0.029, P = 0.029), and urinary albumin excretion (β = 0.033, P = 0.025), irrespective of age, sex, and BMI. Thus, the Chinese-specific low-frequency variant increased the risk of T2D through reducing insulin sensitivity rather than islet β-cell function, which should be considered in the clinical use of GCK activators in the future.

Footnotes

  • This article contains supplementary material online at https://doi.org/10.2337/figshare.13344425.

  • Received May 24, 2020.
  • Accepted December 1, 2020.
  • © 2020 by the American Diabetes Association
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Low-Frequency Genetic Variant in the Hepatic Glucokinase Gene Is Associated With Type 2 Diabetes and Insulin Resistance in Chinese Population
Yumin Ma, Yingying Luo, Siqian Gong, Xianghai Zhou, Yufeng Li, Wei Liu, Simin Zhang, Xiaoling Cai, Qian Ren, Lingli Zhou, Xiuying Zhang, Yanai Wang, Xiuting Huang, Xueying Gao, Mengdie Hu, Xueyao Han, Linong Ji
Diabetes Mar 2021, 70 (3) 809-816; DOI: 10.2337/db20-0564

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Low-Frequency Genetic Variant in the Hepatic Glucokinase Gene Is Associated With Type 2 Diabetes and Insulin Resistance in Chinese Population
Yumin Ma, Yingying Luo, Siqian Gong, Xianghai Zhou, Yufeng Li, Wei Liu, Simin Zhang, Xiaoling Cai, Qian Ren, Lingli Zhou, Xiuying Zhang, Yanai Wang, Xiuting Huang, Xueying Gao, Mengdie Hu, Xueyao Han, Linong Ji
Diabetes Mar 2021, 70 (3) 809-816; DOI: 10.2337/db20-0564
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