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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1476222

Association and function analysis of genetic variants and the risk of Gestational Diabetes Mellitus in a southern Chinese population

Provisionally accepted
Qiulian Liang Qiulian Liang 1Yan Sun Yan Sun 1Ming Li Ming Li 2Ruiqi Li Ruiqi Li 1Lijie Nie Lijie Nie 1Lin Lin Lin Lin 3Xiangyuan Yu Xiangyuan Yu 1*
  • 1 Guilin Medical University, Guilin, China
  • 2 Hunan University of Medicine, Huaihua, Hunan Province, China
  • 3 Fujian Maternity and Child Health Hospital, Fuzhou, Fujian Province, China

The final, formatted version of the article will be published soon.

    Background: Gestational diabetes mellitus (GDM) is a complex metabolic disease, which has short-term and long-term adverse effects on mothers and infants. However, the specific pathogenic mechanism has not been elucidated.Objective: To confirm the associations between candidate genetic variants (rs4134819, rs720918, rs2034410, rs11109509 and rs12524768) and GDM risk and prediction in a southern Chinese population.Methods: Candidate variants were genotyped in 538 GDM cases and 626 healthy controls. The odds ratio (OR) and its corresponding 95% confidence interval (CI) was calculated to assess the associations between genotypes and GDM risk. And then, the false-positive report probability (FPRP) analysis was adopted to confirm the significant associations, and bioinformatics tools were used to explore the potential biological function of studied variants. Finally, risk factors of genetic variants and clinical indicators identified by logistics regression were used to construct a nomogram model for GDM prediction. Results: It was showed that the XAB2 gene rs4134819 was significantly associated with GDM susceptibility (CT vs. CC: adjusted OR=1.38, 95% CI: 1.01-1.87, P=0.044； CT/TT vs. CC: crude OR=1.42, 95% CI: 1.08-1.86, P=0.013). Functional analysis suggested that rs4134819 can alter the specific transcription factors (CPE bind and GATE-1) binding to the promoter of XAB2 gene, regulating the transcription of XAB2. The nomogram established with factors of age, FPG, HbA1c, 1hPG, 2hPG, TG and rs4134819 showed a good discriminated and calibrated ability with an area under the curve (AUC) =0.931 and the Hosmer-Lemeshow test P-value >0.05. Conclusion: The variant rs4134819 can significantly alter the susceptibility of the Chinese population to GDM possibly by regulating the transcription of fuctional genes. The nomogram prediction model constructed with genetic variants and clinical factors can help distinguish high-risk GDM individuals.

    Keywords: gestational diabetes mellitus, genetic variants, Association, Nomogram model, prediction

    Received: 05 Aug 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Liang, Sun, Li, Li, Nie, Lin and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiangyuan Yu, Guilin Medical University, Guilin, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.