Association between TNF-α polymorphisms and gestational diabetes mellitus: a meta-analysis and trial sequential analysis

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.

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

Frontiers in Endocrinology ◽

10.3389/fendo.2021.722674 ◽

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.

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Whether the risk of gestational diabetes mellitus is affected by TNF-α, IL-6, IL-10 or ADIPOQ polymorphisms: a meta-analysis

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-020-00582-8 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Qiqi Huang ◽

Yi Wang ◽

Binbin Gu ◽

Yanwen Xu

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Meta Analysis ◽

Interleukin 10 ◽

Tnf Α ◽

Quantitative Analyses ◽

Factor Α ◽

Positive Results ◽

Necrosis Factor

Abstract Background Whether polymorphisms in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) or adiponectin (ADIPOQ) influence the risk of gestational diabetes mellitus (GDM) or not remain inconclusive. Therefore, the authors conducted a meta-analysis to robustly assess relationships between polymorphisms in TNF-α, IL-6, IL-10 or ADIPOQ and the risk of GDM by merging the results of eligible publications. Methods A through literature searching in Medline, Embase, Wanfang, VIP and CNKI was conducted by the authors to identify eligible publications, and twenty-two publications were finally found to be eligible for merged quantitative analyses. Results The merged quantitative analyses revealed that ADIPOQ + 45T/G (rs2241766) polymorphism was significantly associated with the risk of GDM in overall population (dominant comparison: OR = 0.70, p < 0.001; recessive comparison: OR = 1.95, p < 0.001; over-dominant comparison: OR = 1.18, p = 0.03; allele comparison: OR = 0.71, p < 0.001) and Asians (dominant comparison: OR = 0.70, p < 0.001; recessive comparison: OR = 1.94, p < 0.001; allele comparison: OR = 0.72, p < 0.001). Nevertheless, we did not observe any positive results for TNF-α − 238G/A (rs361525), TNF-α − 308G/A (rs1800629), IL6 − 174G/C (rs1800795), IL-10 − 819C/T (rs1800871), IL-10 − 592C/A (rs1800872), IL-10 − 1082A/G (rs1800896) and ADIPOQ + 276G/T (rs1501299) polymorphisms. Conclusions The present meta-analysis shows that among investigated TNF-α, IL-6, IL-10 or ADIPOQ polymorphisms, only ADIPOQ + 45T/G (rs2241766) polymorphism may affect the risk of GDM.

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