FTO, GCKR, CDKAL1 and CDKN2A/B gene polymorphisms and the risk of gestational diabetes mellitus: a meta-analysis

Arch Gynecol Obstet. 2018 Oct;298(4):705-715. doi: 10.1007/s00404-018-4857-7. Epub 2018 Aug 3.

Abstract

Purpose: Studies had examined the associations between genetic polymorphisms and the risk of gestational diabetes mellitus (GDM). However, conclusions of these studies were controversial due to the smaller sample size and limited statistical power. We carried out a meta-analysis with the aim of providing a more comprehensive summary of the currently available research to evaluate the relationship between FTO, GCKR, CDKAL1 and CDKN2A/B gene polymorphisms and GDM risk.

Methods: Literature search was carried out in the PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wangfang databases up to November 2017. Data were extracted by two independent reviewers and statistical analyses were performed with STATA software. Pooled odds ratios and 95% confidence intervals were calculated by Z test to assess the association between genetic polymorphisms and GDM risk. Stratified analysis was performed based on ethnicity. Heterogeneity and publication bias between studies were evaluated by Cochran's Q test and Egger regression test, respectively.

Results: 14 eligible studies were included. CDKAL1 rs7754840 and rs7756992 showed significant correlation with GDM risk under the allele, recessive, dominant, homozygote and heterozygote models. GCKR rs780094 and CDKN2A/B rs10811661 also showed the same association under the allele, recessive and heterozygote models. No associations between FTO rs9939609 and rs8050136, GCKR rs1260326 and GDM risk were found.

Conclusions: Our meta-analysis showed that two SNPs in particular(rs7754840 and rs7756992 in CDKAL1) were very strongly associated with GDM risk. GCKR rs780094 and CDKN2A/B rs10811661 polymorphisms were moderately associated with GDM risk.

Keywords: CDKAL1; CDKN2A/B; FTO; GCKR; Gene polymorphism; Gestational diabetes mellitus.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Diabetes, Gestational / etiology
  • Diabetes, Gestational / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • tRNA Methyltransferases / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • CDKN2A protein, human
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • GCKR protein, human
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • tRNA Methyltransferases
  • CDKAL1 protein, human