Department of Epidemiology and Health Statistics, Guilin Medical University, Guilin, China.
Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital, Fuzhou, China.
Front Endocrinol (Lausanne). 2021 Oct 14;12:722674. doi: 10.3389/fendo.2021.722674. eCollection 2021.
The CDK5 regulatory subunit-associated protein 1-like 1 () contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current studies on the relationship between polymorphisms rs7756992 A>G and rs7754840 C>G and the risk of gestational diabetes mellitus (GDM) have drawn contradictory conclusions.
A meta-analysis with a fixed- or random-effects model was conducted to estimate the correlation between studied 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.
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 AA: OR = 1.23, 95% CI = 1.08, 1.41, = 0.002; GG AA: OR = 1.47, 95% CI = 1.05, 2.05, = 0.024 for rs7756992; and CG GG: OR = 1.36, 95% CI = 1.13, 1.65, = 0.002; CC GG: OR = 1.76, 95% CI = 1.37, 2.26, < 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.
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.
细胞周期蛋白依赖性激酶 5 调节亚单位相关蛋白 1 样 1（）通过抑制细胞周期蛋白依赖性激酶 5 的激活，有助于胰岛β细胞功能和胰岛素分泌。目前关于 CDK5 调节亚单位相关蛋白 1 样 1 基因多态性 rs7756992 A>G 和 rs7754840 C>G 与妊娠期糖尿病（GDM）风险之间的关系的研究得出了相互矛盾的结论。
采用固定或随机效应模型进行荟萃分析，以估计研究中多态性与 GDM 风险之间的相关性，采用汇总优势比（OR）和 95%置信区间（CI）进行评估。此外，还进行了试验序贯分析（TSA）和假阳性报告概率（FPRP）分析，以确认研究结果。
本研究共纳入 13306 名受试者。Meta 分析结果显示，与野生型 AA 基因型相比，两种多态性的杂合子和纯合子基因型均与 GDM 风险增加相关（AG AA：OR = 1.23，95%CI = 1.08，1.41， = 0.002；GG AA：OR = 1.47，95%CI = 1.05，2.05， = 0.024 用于 rs7756992；CG GG：OR = 1.36，95%CI = 1.13，1.65， = 0.002；CC GG：OR = 1.76，95%CI = 1.37，2.26， < 0.001 用于 rs7754840）。TSA 证实 rs7754840 与 GDM 易感性之间存在显著关联，因为在杂合子和纯合子模型下，累积 Z 曲线穿过了常规截止值和 TSA 边界。
本研究支持 rs7756992 和 rs7754840 与 GDM 易感性相关的发现。然而，需要进一步的功能研究来阐明其机制。
