Association of CDKAL1 rs7754840 with gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Gestational diabetes mellitus (GDM) is a widespread condition during pregnancy with substantial fetal and maternal morbidity. However, the correlation between GDM risk and the CDKAL1 rs7754840 polymorphism is inconsistent.This study aimed to comprehensively evaluate this association through an updated systematic review and meta-analysis.

METHODS

This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. A comprehensive literature search of case-control studies was conducted in CNKI, Embase, PubMed, Scopus, and Web of Science from database inception to December 17, 2025. Five genetic models were selected, along with their odds ratios (ORs) and 95% confidence intervals. Subsequently, stratified analyses were performed by ethnicity and according to diagnostic criteria for GDM. Heterogeneity, publication bias, and trial sequential analysis (TSA) were assessed.

RESULTS

The meta-analysis included 18 studies comprising 8,025 women with GDM and 8,605 controls. Pooled analyses showed an association between the CDKAL1 rs7754840 polymorphism and increased GDM risk, with moderate to substantial between-study heterogeneity across genetic models. Stratified analyses showed consistent associations in Asian populations (15 studies; 7,012 cases/7,921 controls), whereas evidence in Caucasian populations (3 studies; 1,013 cases/684 controls) was inconclusive. Heterogeneity varied across GDM diagnostic criteria, with lower heterogeneity observed among studies using the IADPSG (2010) criteria. TSA showed that the cumulative Z-curve crossed the monitoring boundary but did not reach the required information size, indicating supportive but inconclusive evidence.

CONCLUSIONS

This meta-analysis supports the association between GDM risk and CDKAL1 rs7754840 in Asian populations.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251270398, identifier CRD420251270398.