FTO gene variants (rs9939609, rs8050136 and rs17817449) and type 2 diabetes mellitus risk: A Meta-Analysis

Mohammed Amine Ikhanjal; Mohammed Ali Elouarid; Chaimae Zouine; Houda El Alami; Khaoula Errafii; Hassan Ghazal; Najib Alidrissi; Fadil Bakkali; Adnane Benmoussa; Salsabil Hamdi

doi:10.1016/j.gene.2023.147791

FTO gene variants (rs9939609, rs8050136 and rs17817449) and type 2 diabetes mellitus risk: A Meta-Analysis

Gene. 2023 Dec 15:887:147791. doi: 10.1016/j.gene.2023.147791. Epub 2023 Sep 9.

Authors

Affiliations

¹ Environmental Health Laboratory, Institut Pasteur du Maroc, Morocco; University of Mohamed VI of Sciences and Health, Morocco. Electronic address: mikhanjal@um6ss.ma.
² Environmental Health Laboratory, Institut Pasteur du Maroc, Morocco; University of Mohamed VI of Sciences and Health, Morocco. Electronic address: melouarid2@um6ss.ma.
³ Environmental Health Laboratory, Institut Pasteur du Maroc, Morocco; University of Mohamed VI of Sciences and Health, Morocco. Electronic address: chaimae9725@gmail.com.
⁴ Environmental Health Laboratory, Institut Pasteur du Maroc, Morocco. Electronic address: houdaelalami14@gmail.com.
⁵ African Genomic Center (AGC), University Mohamed VI Polytechnic, Bengurir, Morocco. Electronic address: khaoula.errafii@um6p.ma.
⁶ Laboratory of Genomics, Bioinformatics and Digital Health, School of Medicine, Mohammed VI University of Science and Health, Casablanca, Morocco;s Royal Institute for Management Training, Rabat, Morocco. Electronic address: hassan.ghazal@fulbrightmail.org.
⁷ Department of Surgery and Laboratory of Genomics, Bioinformatics and Digital Health, School of Medicine, Mohammed VI University of Health Sciences, Casablanca, Morocco; Hospital Cheikh Khalifa, Casablanca, Morocco. Electronic address: nalidrissi@um6ss.ma.
⁸ University of Mohamed VI of Sciences and Health, Morocco; Laboratory of toxicology, toxicogenomics and ecotoxicology, University of Mohamed VI of Sciences and Health, Morocco. Electronic address: fbakkali@um6ss.ma.
⁹ University of Mohamed VI of Sciences and Health, Morocco; Laboratory of toxicology, toxicogenomics and ecotoxicology, University of Mohamed VI of Sciences and Health, Morocco. Electronic address: abenmoussa@um6ss.ma.
¹⁰ Environmental Health Laboratory, Institut Pasteur du Maroc, Morocco. Electronic address: Salsabil.hamdi@pasteur.ma.

PMID: 37696421
DOI: 10.1016/j.gene.2023.147791

Abstract

Background and aims: There is tremendous increase in type 2 diabetes mellitus (T2DM) worldwide. The impact of FTO gene polymorphisms on the risk of T2DM is not yet clear because of the controversial results of studies. This meta-analysis aimed to better clarify the association between three FTO gene polymorphisms SNPs (rs9939609, rs8050136 and rs17817449) and T2DM in a larger combined population worldwide.

Material and methods: A comprehensive search on the PubMed, Science Direct, and Web of Science databases was conducted to identify investigations in relationship between different FTO gene polymorphisms (rs9939609, rs8050136 and rs17817449) and T2DM globally. Published papers from January 2007 to May 2023 were collected. Inclusion criteria are limited to human case-control studies published in English and peer-reviewed, which provided data on the genotype distributions of FTO gene polymorphisms and T2DM risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the results of the meta-analysis. Potential sources of bias and heterogeneity using Egger's regression analysis were also assessed.

Results: Of 234695 identified articles, forty-eight studies were selected including 36,051 patients with T2DM and 51,266 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and rs9939609 FTO gene polymorphism in the Allele contrast (A vs. T: OR = 1,30, 95% CI = 1.14; 1.48, P < 0,05, I² = 0,94), Recessive model (AA vs. AT + TT: OR = 1,54, 95% CI = 1.19; 2.00, P < 0,05, I² = 0,94), Dominant model (AA + AT vs. TT: OR = 1,26, 95% CI = 1.10; 1.45, P < 0,05, I² = 0,89), homozygote model (AA vs. TT: OR = 1,60, 95% CI = 1.26; 2.03, P < 0,05, I² = 0,90), and heterozygote model (AA vs. AT: OR = 1,43, 95% CI = 1.09; 1.88, P = 0,008, I² = 0,93). we also found a significantly increased risk of T2DM susceptibility and rs8050136 FTO gene polymorphism under all models. For rs17817449 we did not find any association between with T2DM.

Conclusion: The present meta-analysis confirms that rs9939609 and rs8050136 in the FTO gene are significantly associated with T2DM, while rs17817449 does not show any association.

Keywords: FTO; Meta-analysis; SNPs; Type 2 diabetes mellitus.

Publication types

Meta-Analysis

MeSH terms

Alleles
Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
Case-Control Studies
Diabetes Mellitus, Type 2* / genetics
Genotype
Humans
Polymorphism, Single Nucleotide

Substances

FTO protein, human
Alpha-Ketoglutarate-Dependent Dioxygenase FTO