Diabetology & Metabolic Syndrome (Dec 2022)

Genetic variants of the GLP-1R gene affect the susceptibility and glucose metabolism of gestational diabetes mellitus: a two-center nested case‒control study

  • Ping Luo,
  • Ying Fan,
  • Yusha Xiong,
  • Hua Feng,
  • Zhiping Yang,
  • Chunlin Zhang,
  • Bing Mei

DOI
https://doi.org/10.1186/s13098-022-00963-1
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 15

Abstract

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Abstract Background Gestational diabetes mellitus (GDM) is the most common complication during pregnancy, occurring under the combined action of environmental and genetic factors. Genetic variants of glucagon-like peptide-1 receptor (GLP-1R) have been reported to affect insulin secretion and susceptibility to type 2 diabetes. This study aimed to explore the role of GLP-1R polymorphisms in GDM and glucose metabolism. Methods A two-center nested case‒control study was designed, including 200 pregnant women with GDM and 200 pregnant women without GDM genotyped for five tag SNPs of GLP-1R using Sanger sequencing. Logistic regression was used to evaluate the relationship between GLP-1R polymorphisms and GDM risk. Glucose and insulin concentrations were measured based upon the 75 g oral glucose tolerance test (OGTT). Beta cell function of different genotypes was estimated with the 60 min insulinogenic index (IGI60) and OGTT-derived disposition index (DI). Results Mutant genotype AG + GG of tag SNP rs6458093 nominally increased GDM risk (p = 0.049), especially among subjects younger than 35 years (p = 0.024) and with BMI no less than 24 (p = 0.041), after adjusting for confounders. Meanwhile, compared with subjects with wild genotype AA, subjects with genotype AG + GG of rs6458093 also showed nominally significantly lower IGI60 (p = 0.032) and DI (p = 0.029), as well as significantly higher 75 g OGTT-based 1 h glucose load plasma glucose levels (p = 0.045). Moreover, the mutant heterozygous genotype GA of tag SNP rs3765467 nominally decreased GDM risk among subjects older than 35 years (p = 0.037) but showed no association with insulin secretion and glucose homeostasis. Conclusions Tag SNP rs6458093 of GLP-1R was nominally associated with increased GDM risk and affected beta cell function and postprandial glucose metabolism, while tag SNP rs3765467 of GLP-1R was nominally associated with decreased GDM risk, providing evidence for molecular markers and etiological study of GDM.

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