FTO Gene Polymorphisms and Their Impact on Cardiovascular Disease and Coronary Artery Anatomy: A Systematic Review and Meta-Analysis

Venkateswarlu Yadavalli 1 * , Anbalagan Gnanavel 2, Saravanakumar Sundaresan 2, Praveen Thammisetti 3, Karthick Selvaraj 4
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1 PhD Program, Department of Anatomy Meenakshi academy of higher education and research, Chennai, India
2 Department of Anatomy, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research Institute, Kanchipuram, India
3 Department of Anatomy, Ayaan Institute of Medical Science, Kanaka Mamidi, Moinabad, Ranga Reddy District, Telangana, India
4 Head of Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research Institute, Kanchipuram, India
* Corresponding Author
J CLIN MED KAZ, Volume 23, Issue 1, pp. 69-78. https://doi.org/10.23950/jcmk/17448
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Author Contributions: Conceptualization, Y.V.; methodology, Y.V. and G.A.; validation, T.P. and K.S.; formal analysis, G.A., S.S., T.P., and K.S.; investigation, Y.V. and G.A.; resources, S.S. and T.P.; data curation, T.P. and K.S.; writing – original draft preparation, Y.V. and G.A.; writing – review and editing,  Y.V. and G.A., G.A., S.S., T.P., and K.S.; visualization, Y.V. and G.A.; supervision, AG and K.S.; project administration, Y.V.; funding acquisition, Y.V. All authors have read and agreed to the published version of the manuscript.

Data availability statement: The corresponding author can provide the data supporting the study's conclusions upon request. Due to ethical and privacy constraints, the data are not publicly accessible.

Artificial Intelligence (AI) Disclosure Statement: AI-Unassisted Work.

ABSTRACT

Background: Genetic polymorphism of the fat mass and obesity-associated (FTO) gene, i.e., rs9939609 and rs1121980, was previously thought to be responsible for the pathophysiologies of obesity, metabolic syndrome, and cardiovascular disease (CVD). No strong association of the polymorphisms with vascular properties like transluminal diameter and coronary artery anatomy in populations has been reported despite numerous previous studies. To critically evaluate the interaction of FTO gene polymorphisms with cardiovascular/metabolic events, coronary artery morphology, and demographic diversity at the tertiary level.
Methods: Systematic searching in PubMed, Embase, Web of Science, Scopus, and Google Scholar up to July 2025. 1,265 records were searched, and 33 studies were screened and evaluated in full-text evaluation, of which 25 studies were included in the meta-analysis. Exposure characteristics, including SNP variant, endpoint, ethnicity, and type of genotyping, were defined. Statistical power in studies was estimated using Quanto software. Pooled odds ratios (OR) and their 95% confidence intervals (CIs) were calculated from the random-effects model. Subgroup analysis by ethnicity, outcome group, and study quality was conducted.
Results: Meta-analysis identified FTO rs9939609 risk allele A to be strongly related to CVD risk (pooled OR = 1.29, 95% CI: 1.15–1.44, p < 0.001). The association was consistent in European (OR = 1.33), East Asian (OR = 1.24), and South Asian individuals (OR = 1.21). In the subgroup analysis, the augmented effects were in the combined endpoint obesity-CVD studies and TaqMan genotyping. FTO alleles were associated with transluminal narrowing reported in isolated individual trials, a majority of which were among obese CAD patients. There was no homogeneous socioeconomic context report, but combined data were given for possible gene-environment interaction with vascular anatomy.
Conclusion: FTO gene polymorphisms, and particularly rs9939609, have been linked with cardiovascular risk and may influence coronary artery structure, particularly in metabolically vulnerable individuals. Gene screening within the process of CVD risk stratification, particularly in demographically heterogeneous practice, is justified by the findings.
Keywords: FTO gene, rs9939609, coronary artery disease, cardiovascular risk, transluminal diameter, genotyping, meta-analysis, polymorphism.

CITATION

Yadavalli V, Gnanavel A, Sundaresan S, Thammisetti P, Selvaraj K. FTO Gene Polymorphisms and Their Impact on Cardiovascular Disease and Coronary Artery Anatomy: A Systematic Review and Meta-Analysis. J CLIN MED KAZ. 2026;23(1):69-78. https://doi.org/10.23950/jcmk/17448

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