Journal of Diabetes Investigation (Nov 2021)

Novel association between a transient receptor potential cation channel subfamily M member 5 expression quantitative trait locus rs35197079 and decreased susceptibility of gestational diabetes mellitus in a Chinese population

  • Xi Li,
  • Liping Lai,
  • Jindi Su,
  • Shiguo Chen,
  • Sheng Lin,
  • Baojiang Wang,
  • Jian Gao,
  • Linghua Zhang,
  • Keqin Yao,
  • Shan Duan

DOI
https://doi.org/10.1111/jdi.13572
Journal volume & issue
Vol. 12, no. 11
pp. 2062 – 2070

Abstract

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Abstract Aims/Introduction Emerging evidence suggests that expression quantitative trait loci (eQTLs) are more likely to associate with complex diseases. Transient receptor potential cation channel subfamily M member 5 (TRPM5) is a ubiquitously expressed voltage‐gated cation channel that acts indispensably to trigger insulin secretion in pancreatic β‐cells. The present study evaluated the association between TRPM5 eQTL single‐nucleotide polymorphisms and the risk of gestational diabetes mellitus (GDM) in a Chinese population. Materials and Methods A total of 380 unrelated Chinese pregnant women including 241 GDM patients and 139 controls were included in this study. The eQTL single‐nucleotide polymorphisms of TRPM5 were obtained from the GTEx eQTL Browser, and were subsequently genotyped using the Agena MassARRAY iPLEX platform. Results Logistic regression analysis and linear regression analysis showed that rs35197079 and rs74848824 were significantly associated with reduced GDM risk and lower fasting plasma glucose levels after adjusting confounder factors in dominant genetic models. Stratification analysis based on pre‐pregnancy body mass index validated a strong association between rs35197079 and GDM susceptibility in underweight and normal weight individuals. Luciferase and electrophoretic mobility shift assays carried out in rat pancreatic β‐cells showed that rs35197079 was functional. Conclusions The TRPM5 eQTL single‐nucleotide polymorphism rs35197079 was associated with decreased GDM susceptibility in a Chinese population, especially in underweight and normal weight pregnant women, and it was functional in modulating gene transcription.

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