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Higher risk of metabolic syndrome in children and adolescents and polymorphisms in the fat mass and obesity-associated gene: a systematic review and meta-analysis

Pediatric Research (2025)Cite this article

Abstract

Background

The relationship between polymorphisms in fat mass and obesity-associated gene (FTO) and the components of metabolic syndrome (MetS) has been explored among children and adolescents, but the results are inconsistent and inconclusive.

Methods

Electronic databases including Medline, Scopus, Embase, Web of Science, CNKI, and Google Scholar were searched for eligible studies, and data were extracted from each study. Standardized mean differences were calculated to examine the differences in the components of MetS between FTO genotypes.

Results

Forty-six studies (45,100 subjects), seven studies (4216 subjects), and six studies (2699 subjects) were included in the meta-analyses for FTOrs9939609, FTOrs1421085, and FTOrs17817449 polymorphisms, respectively. A-allele carriers of FTOrs9939609 polymorphism had higher levels of waist circumference (WC), systolic blood pressure, and fasting blood glucose, but lower levels of high-density lipoprotein cholesterol (HDL-C) than TT homozygotes (pā€‰<ā€‰0.05 for all). C-allele carriers of FTOrs1421085 polymorphism had higher levels of WC and lower levels of HDL-C than TT homozygotes (pā€‰<ā€‰0.05 for both). No significant associations between FTOrs17817449 polymorphism and the components of MetS were detected.

Conclusion

The meta-analysis demonstrates that A allele of FTOrs9939609 and C allele of FTOrs1421085 polymorphisms confer a higher risk of MetS among children and adolescents.

Impact statement

Genetic polymorphisms are closely related to metabolic syndrome in children and adolescents. The rs9939609 polymorphism in fat mass and obesity-associated gene is apparently associated with a higher risk of metabolic syndrome among children and adolescents. The findings of this study can provide reference for gene diagnosis and gene therapy of metabolic syndrome in children and adolescents.

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Fig. 1
Fig. 2: Forest plot of the association analysis between FTOrs9939609 polymorphism and WC.
Fig. 3: Forest plot of the association analysis between FTOrs9939609 polymorphism and SBP.
Fig. 4: Forest plot of the association analysis between FTOrs9939609 polymorphism and FBG.
Fig. 5: Forest plot of the association analysis between FTOrs9939609 polymorphism and HDL-C.

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Funding

The project was supported by the Natural Science Foundation of Sichuan, China [2024NSFSC0657], the Research Project of Clinical Medical College & Affiliated Hospital of Chengdu University [YYB2017002], and the Research Project of Clinical Medical College & Affiliated Hospital of Chengdu University [Y202204].

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  1. These authors contributed equally: Yongyan Song, Shujin Li.

Authors and Affiliations

  1. Central Laboratory, Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu, Sichuan, PR China

    Yongyan SongĀ &Ā Shujin Li

  2. Clinical Medical College of Chengdu University, Chengdu, Sichuan, PR China

    Hao Liu,Ā Xinyu LiuĀ &Ā Jing Li

  3. Department of Urology Surgery, Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu, Sichuan, PR China

    Yunhan WangĀ &Ā Jin Yang

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Contributions

Yang J, Song YY, and Li SJ conceived of the systematic review and meta-analysis, participated in the design, analyzed the data, and drafted the manuscript. Li SJ, Liu H, Liu XY, Li J, and Wang YH carried out the literature search, collected the data, and revised the manuscript critically for important intellectual content. All authors reviewed and approved the final version of the manuscript for submission.

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Correspondence to Jin Yang.

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Song, Y., Li, S., Liu, H. et al. Higher risk of metabolic syndrome in children and adolescents and polymorphisms in the fat mass and obesity-associated gene: a systematic review and meta-analysis. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04020-1

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  • DOI: https://doi.org/10.1038/s41390-025-04020-1

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