ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
FTO rs9939609 and rs17817449 polymorphisms contribute to metabolic syndrome risk by increasing triglyceride and glucose levels
Provisionally accepted
- 1Affiliated Hospital and Clinical Medical College of Chengdu University, Chengdu, China
- 2Chengdu University, Chengdu, China
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Background and Aims: The polymorphisms in fat mass and obesity-associated gene (FTO) have been implicated in metabolic dysregulation. This study aimed to investigate the associations between the FTO rs9939609 and rs17817449 polymorphisms and MetS risk, and to assess whether glucolipid parameters mediate these associations. Methods: A hospital-based cross-sectional study involving 701 adults was conducted. MetS was diagnosed according to the criteria of the International Diabetes Federation (2005). Clinical data were collected for all participants. Genotyping of rs9939609 and rs17817449 was performed via polymerase chain reaction-restriction fragment length polymorphism. Logistic regression and mediation analysis were used to evaluate genetic associations and mediating effects. Results: The MetS group showed higher frequencies of rs9939609 A allele (14.01% vs. 6.09%, P < 0.001) and rs17817449 G allele (16.94% vs. 12.18%, P = 0.012) compared to controls. Rs9939609 AA genotype carriers had the highest MetS risk (OR = 3.58, 95% CI: 1.08–11.88) and exhibited allelic dose-dependent worsening of triglycerides, high-density lipoprotein cholesterol (HDL-C), and fasting blood glucose (FBG) (all P < 0.05). Similarly, rs17817449 G allele was linked to elevated triglycerides, reduced HDL-C, higher FBG, and increased systolic blood pressure (all P < 0.05). Mediation analysis revealed triglycerides, HDL-C, and FBG as significant mediators for the associations of rs9939609 and rs17817449 with MetS (all P < 0.001). Conclusions: FTO rs9939609 and rs17817449 polymorphisms are strongly associated with MetS risk, primarily by increasing triglyceride and glucose levels and decreasing HDL-C. These findings highlight the pivotal role of FTO variants in metabolic dysregulation and suggest potential targets for early intervention of MetS.
Keywords: FTO, polymorphism, rs9939609, Rs17817449, metabolic syndrome
Received: 04 Jul 2025; Accepted: 07 Nov 2025.
Copyright: © 2025 Song, Wang, Su, Wang, Zhang, Pan, Yunhan and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jin Yang, yangjin@cdu.edu.cn
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