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Association of rs9939609 of the FTO Gene with Obesity Phenotypes in Women

https://doi.org/10.31550/1727-2378-2025-24-4-43-50

Abstract

Aim. To study the association of rs9939609 of the FTO gene with various obesity phenotypes, its individual parameters, and some risk factors in a sample of women

Design. Cross-sectional cohort study.

Materials and methods. The study was conducted on the basis of the population sample of the HAPIEE project, the age of the participants was — 45–69 years (n = 1036). Groups of women were formed, selected by body mass index (BMI) using the criteria of the World Health Organization. DNA was isolated from blood using the phenol-chloroform extraction method. Genotyping of the rs9939609 gene FTO was performed using polymerase chain reaction (PCR) with restriction fragment length polymorphism and real-time PCR (TaqMan probes). The frequency of genotypes in groups with different BMI, with different body roundness indexes (BRI), waist and hip circumference; with morbid obesity (MO) and abdominal obesity (AO) was analyzed.

Results. When comparing the frequencies of the A allele (AA and AT genotypes) and the TT genotype in groups with different BMIs, significant differences were obtained (p = 0.007). The highest frequency of the TT genotype (38.5%) was in the group of women with a BMI of 18.5 to 24.9 kg/m2, the  lowest (23.5%) — with a BMI of 35 to 39.9 kg/m2. In this group, the AA genotype was most common. The frequency of carriage of the AT genotype increased nonlinearly with increasing BMI. The statistical significance of differences in BMI between carriers of different genotypes according to the Kruskal — Wallis — test is less than 0.001. Significant differences were also observed in waist (p = 0.001) and hip (p < 0.001) circumferences — the smallest in carriers of the TT genotype. In univariate logistic regression analysis with age-adjusted adjustment, the odds ratio (OR) of having MO in the AA genotype — 1.80 (95% confidence interval (CI): 1.09–2.95; p = 0.021), in the AT genotype — 1.82 (95% CI: 1.23–2.68; p = 0.002), and in the TT genotype — 0.56 (95% CI: 0.39–0.81; p = 0.002). In the univariate logistic regression analysis with age-adjusted analysis, the significance of the TT genotype carriage as a conditionally protective factor in relation to the development of MO (OR = 0.56; 95% CI: 0.34–0.91; p = 0.021) and AO (OR = 0.65; 95% CI: 0.45–0.94; p = 0.023) was preserved, as was the increased probability of AO in carriers of the AT genotype (OR = 1.53; 95% CI: 1.15–2.02; p = 0.003) and AA genotype (OR = 1.54; 95% CI: 1.06–2.23; p = 0.023).

Conclusion. Carriage of the A allele of rs9939609 of the FTO gene is an important factor associated with various obesity phenotypes in women. Due to the diversity of factors associated with obesity, it is necessary to continue research in this area to develop effective personalized preventive and therapeutic strategies.

About the Authors

V. N. Maksimov
Research Institute of Internal and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

Novosibirsk



S. Minnikh
Research Institute of Internal and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

Novosibirsk



Yu. V. Ivanova
Research Institute of Internal and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

Novosibirsk



E. S. Shabanova
Research Institute of Internal and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

Novosibirsk



O. D. Rymar
Research Institute of Internal and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

Novosibirsk



S. K. Malyutina
Research Institute of Internal and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation

Novosibirsk



References

1. Frayling T.M., Timpson N.J., Weedon M.N., Zeggini E. et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889–94. DOI: 10.1126/science.1141634

2. Denisova D.V., Gurazheva A.A., Maximov V.N. Associations of polymorphisms of some genes with excessive weight in a population sample of young citizens of Novosibirsk. Ateroscleroz. 2021;17(4):35–42. (in Russian). DOI: 10.52727/2078-256X-2021-17-4-35-42

3. Sierra-Ruelas E., Campos-Pérez W., Torres-Castillo N., GarcíaSolís P. et al. The rs9939609 variant in FTO increases the risk of hypercholesterolemia in metabolically healthy subjects with excess weight. Lifestyle Genom. 2022;15(4):131–8. DOI: 10.1159/000527097

4. Speakman J.R. The 'Fat Mass and Obesity Related' (FTO) gene: mechanisms of impact on obesity and energy balance. Curr. Obes. Rep. 2015;4(1):73–91. DOI: 10.1007/s13679-015-0143-1

5. Liu S., Song S., Wang S., Cai T. et al. Hypothalamic FTO promotes high-fat diet-induced leptin resistance in mice through increasing CX3CL1 expression. J. Nutr. Biochem. 2024;123:109512. DOI: 10.1016/j.jnutbio.2023.109512

6. Huđek A., Škara L., Smolkovič B., Kazazić S. et al. Higher prevalence of FTO gene risk genotypes AA rs9939609, CC rs1421085, and GG rs17817449 and saliva containing Staphylococcus aureus in obese women in Croatia. Nutr. Res. 2017;50:94–103. DOI: 10.1016/j.nutres.2017.12.005

7. Yin D., Li Y., Liao X., Tian D. et al. FTO: a critical role in obesity and obesity-related diseases. Br. J. Nutr. 2023;130(10):1657–64. DOI: 10.1017/S0007114523000764

8. Nindrea R.D., Thongwichian P. FTO gene polymorphisms rs9939609 and the risk of obesity among adults in Western and Asian countries: a systematic review and meta-analysis. Clin. Epidemiol. Global Health. 2024;27:101621. DOI: 10.1016/j.cegh.2024.101621

9. Pledger S.L., Ahmadizar F. Gene-environment interactions and the effect on obesity risk in low and middle-income countries: a scoping review. Front. Endocrinol. (Lausanne). 2023;14:1230445. DOI: 10.3389/fendo.2023.1230445

10. Piwonska A.M., Cicha-Mikolajczyk A., Sobczyk-Kopciol A., Piwonski J. et al. Independent association of FTO rs9939609 polymorphism with overweight and obesity in Polish adults. Results from the representative population-based WOBASZ study. J. Physiol. Pharmacol. 2022;73(3). DOI: 10.26402/jpp.2022.3.07

11. Maksimov V.N., Orlov P.S., Ivanova А.А., Lozhkina N.G. et al. Complex evaluation of the significance of populational genetic markers associated with myocardial infarction and risk factors Russian Journal of Cardiology. 2017;10(150):33–41. (in Russian). DOI: 10.15829/1560-4071-2017-10-33-41

12. Boyarinova M.A., Rotar O.P., Kostareva A.A., Khromova N.V. et al. Association between the FTO gene rs9939609 polymorphism and metabolic health in obese patients living in St. Petersburg. Doctor.Ru. 2018;8(152):20–4. (in Russian). DOI: 10.31550/1727-2378-2018-152-8-20-24

13. Rubino F., Cummings D.E., Eckel R.H., Cohen R.V. et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025;13(3):221–62. DOI: 10.1016/S2213-8587(24)00316-4

14. Peasey A., Bobak M., Kubinova R., Malyutina S. et al. Determinants of cardiovascular disease and other non-communicable diseases in Central and Eastern Europe: rationale and design of the HAPIEE study. BMC Public Health. 2006;6(1):255.

15. Ametov A.S. Metabolic health and obesity: prospects and challenges. Doctor.Ru. 2024;23(8):9–14. (in Russian). DOI: 10.31550/1727-2378-2024-23-8-9-14

16. Smith G.I., Mittendorfer B., Klein S. Metabolically healthy obesity: facts and fantasies. J. Clin. Invest. 2019;129(10):3978–89. DOI: 10.1172/JCI129186

17. Thomas D.M., Bredlau C., Bosy-Westphal A., Mueller M. et al. Relationships between body roundness with body fat and visceral adipose tissue emerging from a new geometrical model. Obesity (Silver Spring). 2013;21(11):2264–71. DOI: 10.1002/oby.20408

18. Zhang X., Ma N., Lin Q., Chen K. et al. Body roundness index and all-cause mortality among US adults. JAMA Netw. Open. 2024;7(6):e2415051. DOI: 10.1001/jamanetworkopen.2024.15051. Erratum in: JAMA Netw. Open. 2024;7(7):e2426540. DOI: 10.1001/jamanetworkopen.2024.26540

19. Zimmermann E., Ängquist L.H., Mirza S.S., Zhao J.H. et al. Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults. Obes. Rev. 2015;16(4):327–40. DOI: 10.1111/obr.12263

20. Goni L., García-Granero M., Milagro F.I., Cuervo M. et al. Phenotype and genotype predictors of BMI variability among European adults. Nutr. Diabetes. 2018;8(1):27. DOI: 10.1038/s41387-018-0041-1

21. Duarte M.R., de Moraes Heredia A.S., Arantes V.C., de Barros Reis M.A. et al. The interaction of the FTO gene and age interferes with macronutrient and vitamin intake in women with morbid obesity. Exp. Gerontol. 2024;193:112463. DOI: 10.1016/j.exger.2024.112463

22. Chiang K.M., Chang H.C., Yang H.C., Chen C.H. et al. Genome-wide association study of morbid obesity in Han Chinese. BMC Genet. 2019;20(1):97. DOI: 10.1186/s12863-019-0797-x

23. Park H.G., Choi J.H. Genetic variant rs9939609 in FTO is associated with body composition and obesity risk in Korean females. BMJ Open Diabetes Res. Care. 2023;11(6):e003649. DOI: 10.1136/bmjdrc-2023-003649

24. Iłowiecka K., Glibowski P., Libera J., Koch W. Changes in novel anthropometric indices of abdominal obesity during weight loss with selected obesity-associated single-nucleotide polymorphisms: a small one-year pilot study. Int. J. Environ. Res. Public Health. 2022;19(18):11837. DOI: 10.3390/ijerph191811837


Review

For citations:


Maksimov V.N., Minnikh S., Ivanova Yu.V., Shabanova E.S., Rymar O.D., Malyutina S.K. Association of rs9939609 of the FTO Gene with Obesity Phenotypes in Women. Title. 2025;24(4):43-50. (In Russ.) https://doi.org/10.31550/1727-2378-2025-24-4-43-50

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