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

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiang-yuan Yu ◽  
Li-ping Song ◽  
Shu-dan Wei ◽  
Xiao-lan Wen ◽  
Da-bin Liu
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Sequential Analysis ◽  
Cell Function ◽  
Meta Analysis ◽  
Regulatory Subunit ◽  
Trial Sequential Analysis ◽  
Functional Studies ◽  
Β Cell Function

ObjectivesThe 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 MethodsA 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.ResultsA 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.ConclusionsThis study supported the finding that rs7756992 and rs7754840 are associated with susceptibility to GDM. However, further functional studies are warranted to clarify the mechanism.

scholarly journals Lack of association between IGF2BP2 rs4402960 polymorphism and gestational diabetes mellitus: a case–control study, meta-analysis and trial sequential analysis

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Jing Liu ◽  
Guang Song ◽  
Ge Zhao ◽  
Tao Meng
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Sequential Analysis ◽  
Case Control Study ◽  
Meta Analysis ◽  
Case Control ◽  
Genetic Models ◽  
Trial Sequential Analysis ◽  
Control Study

Abstract Background: It is well known that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs4402960 polymorphism is associated with Type 2 diabetes mellitus, which has a shared genetic background with gestational diabetes mellitus (GDM). Previous studies have yielded controversial results about the link between IGF2BP2 rs4402960 polymorphism and GDM risk. Thus, a meta-analysis was performed to obtain more conclusive results. Methods: Clinical and genotype data were determined for 305 GDM and 1216 healthy participants recruited. Eligible studies were retrieved in PubMed, Web of science, EMBASE, and Scopus. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to evaluate the relationship between IGF2BP2 polymorphisms and GDM susceptibility in five genetic models. The subgroup stratified analysis and trial sequential analysis (TSA) were performed. Results: In this case–control study, no significant association was revealed between IGF2BP2 polymorphism and GDM (P>0.05). When combined with the previous studies in the meta-analysis, there was no statistical association between IGF2BP2 polymorphism and GDM (allele model: OR = 1.01, 95% CI = 0.86–1.18; dominant model: OR = 1.00, 95% CI = 0.81–1.24; recessive model: OR = 1.08, 95% CI = 0.91–1.29; heterozygous model: OR = 0.99, 95% CI = 0.80–1.24; homozygous model: OR = 1.06, 95% CI = 0.78–1.42). No association was observed in five genetic models in each subgroup. TSA indicated sufficient proof of such null association in the overall population. Conclusions: This meta-analysis provides sufficient statistical evidence indicating null association between IGF2BP2 rs4402960 polymorphism and GDM risk.

microRNA‐96 protects pancreatic β‐cell function by targeting PAK1 in gestational diabetes mellitus

BioFactors ◽  
2018 ◽  
Vol 44 (6) ◽  
pp. 539-547 ◽  
Author(s):  
Lei Li ◽  
Shan Wang ◽  
Hongyan Li ◽  
Jipeng Wan ◽  
Qian Zhou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

2019 ◽  
Vol 20 (24) ◽  
pp. 6171 ◽  
Author(s):  
Petra I. Lorenzo ◽  
Alejandro Martín-Montalvo ◽  
Nadia Cobo Vuilleumier ◽  
Benoit R. Gauthier
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cell Function ◽  
Cell Mass ◽  
Late Pregnancy ◽  
Adverse Outcomes ◽  
Β Cell ◽  
Β Cell Function ◽  
Pax Family

Gestational diabetes mellitus (GDM), a metabolic disease that develops with the increase in insulin resistance during late pregnancy, is currently one of the most common complications affecting pregnancy. The polygenic nature of GDM, together with the interplay between different genetic variants with nutritional and environmental factors has hindered the full understanding of the etiology of this disease. However, an important genetic overlap has been found with type 2 diabetes mellitus (T2DM) and, as in the case of T2DM, most of the identified loci are associated with β-cell function. Early detection of GDM and adequate interventions to control the maternal glycemia are necessary to avoid the adverse outcomes for both the mother and the offspring. The in utero exposure to the diabetic milieu predispose these children for future diseases, among them T2DM, originating a vicious circle implicated in the increased prevalence of both GDM and T2DM. The involvement of inflammatory processes in the development of GDM highlights the importance of pancreatic β-cell factors able to favor the adaptation processes required during gestation, concomitantly with the protection of the islets from an inflammatory milieu. In this regard, two members of the Pax family of transcription factors, PAX4 and PAX8, together with the chromatin remodeler factor HMG20A, have gained great relevance due to their involvement in β-cell mass adaptation together with their anti-inflammatory properties. Mutations in these factors have been associated with GDM, highlighting these as novel candidates for genetic screening analysis in the identification of women at risk of developing GDM.

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