Type 2 diabetes linked FTO gene variant rs8050136 is significantly associated with gravidity in gestational diabetes in a sample of Bangladeshi women: Meta-analysis and case-control study

PLoS One. 2023 Nov 30;18(11):e0288318. doi: 10.1371/journal.pone.0288318. eCollection 2023.

Abstract

Objective: Gestational diabetes mellitus (GDM) is a growing public health concern that has not been extensively studied. Numerous studies have indicated that a variant (rs8050136) of the fat mass-associated gene, FTO, is associated with both GDM and Type 2 diabetes mellitus(T2DM). We conducted a meta-analysis on the association between the FTO single nucleotide polymorphism (SNP) rs8050136 and T2DM, followed by a case-control study on the association of the said SNP and GDM in a sample of Bangladeshi women.

Method: A total of 25 studies were selected after exploring various databases and search engines, which were assessed using the Newcastle-Ottawa Scale (NOS). The MetaGenyo web tool was used to conduct this meta-analysis. A case-control study was performed on 218 GDM patients and 284 controls to observe any association between FTO rs8050136 and GDM. Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS) method, and statistical analyses were performed using various statistical softwares.

Results: In the meta-analysis 26231 cases and 43839 controls were examined. Pooled association analyses revealed a statistically significant relationship between the FTO rs8050136 polymorphism and an elevated risk of T2DM under all genetic models (P<0.05). In the case-control study, synergistic analyses of the SNP and gravida with GDM revealed a significant (P<0.01) association with an increase in odds by 1.6 to 2.4 folds in multigravida and decrease in odds by 2 folds in primigravida. A positive family history of diabetes and the minor allele of this SNP collectively increased the risk of developing GDM by many-fold (1.8 to 2.7 folds). However, after accounting for family history of diabetes and gravidity, analyses showed no significant association with GDM.

Conclusion: Our meta-analysis revealed a significant association between SNP rs8050136 of FTO with T2DM, and this variant was substantially associated with an increased risk of GDM in a sample of Bangladeshi multigravida women.

Publication types

  • Meta-Analysis

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Case-Control Studies
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes, Gestational* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Gravidity
  • Humans
  • Polymorphism, Single Nucleotide
  • Pregnancy

Substances

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human

Grants and funding

The work has been supported by the fund of Special allocation of Ministry of Science and Technology(https://most.gov.bd/), Government of the people’s Republic of Bangladesh in the fiscal year of 2014-15. The project ID was MEDI; S- 19. SM received this fund. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.