Objectives: The CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current studies on the relationship between CDKAL1 polymorphisms rs7756992 A>G and rs7754840 C>G and the risk of gestational diabetes mellitus (GDM) have drawn contradictory conclusions.
Materials and methods: A meta-analysis with a fixed- or random-effects model was conducted to estimate the correlation between studied CDKAL1 polymorphisms and GDM risk with the summary odds ratio (OR) and 95% confidence interval (CI). In addition, trial sequential analysis (TSA) and false-positive report probability (FPRP) analysis were performed to confirm the study findings.
Results: A total of 13,306 subjects were included in the present study. Meta-analysis results showed that the variant heterozygous and homozygous genotypes of the two polymorphisms were associated with increased GDM risk in comparison with the wild-type AA genotype (AG vs. AA: OR = 1.23, 95% CI = 1.08, 1.41, p = 0.002; GG vs. AA: OR = 1.47, 95% CI = 1.05, 2.05, p = 0.024 for rs7756992; and CG vs. GG: OR = 1.36, 95% CI = 1.13, 1.65, p = 0.002; CC vs. GG: OR = 1.76, 95% CI = 1.37, 2.26, p < 0.001 for rs7754840). The TSA confirmed a significant association between rs7754840 and the susceptibility to GDM because the cumulative Z-curve crossed both the conventional cutoff value and the TSA boundaries under the heterozygote and homozygote models.
Conclusions: This study supported the finding that rs7756992 and rs7754840 are associated with susceptibility to GDM. However, further functional studies are warranted to clarify the mechanism.
Keywords: false-positive report probability; gestational diabetes mellitus (GDM); meta-analysis; polymorphism; trial sequential analysis (TSA).
Copyright © 2021 Yu, Song, Wei, Wen and Liu.