AUTHOR=Yu Xiang-yuan , Song Li-ping , Wei Shu-dan , Wen Xiao-lan , Liu Da-bin 

TITLE=CDK5 Regulatory Subunit-Associated Protein 1-Like 1 Gene Polymorphisms and Gestational Diabetes Mellitus Risk: A Trial Sequential Meta-Analysis of 13,306 Subjects

JOURNAL=Frontiers in Endocrinology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.722674

DOI=10.3389/fendo.2021.722674

ISSN=1664-2392

ABSTRACT=<sec><title>Objectives</title><p>The CDK5 regulatory subunit-associated protein 1-like 1 (<italic>CDKAL1</italic>) contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current studies on the relationship between <italic>CDKAL1</italic> polymorphisms rs7756992 A&gt;G and rs7754840 C&gt;G and the risk of gestational diabetes mellitus (GDM) have drawn contradictory conclusions.</p></sec><sec><title>Materials and Methods</title><p>A meta-analysis with a fixed- or random-effects model was conducted to estimate the correlation between studied <italic>CDKAL1</italic> 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.</p></sec><sec><title>Results</title><p>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 <italic>vs.</italic> AA: OR = 1.23, 95% CI = 1.08, 1.41, <italic>p</italic> = 0.002; GG <italic>vs.</italic> AA: OR = 1.47, 95% CI = 1.05, 2.05, <italic>p</italic> = 0.024 for rs7756992; and CG <italic>vs.</italic> GG: OR = 1.36, 95% CI = 1.13, 1.65, <italic>p</italic> = 0.002; CC <italic>vs.</italic> GG: OR = 1.76, 95% CI = 1.37, 2.26, <italic>p</italic> &lt; 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.</p></sec><sec><title>Conclusions</title><p>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.</p></sec>