Polymorphism of the PPARG, AGTR1, VEGF-A genes: frequency and association with obesity phenotypes
https://doi.org/10.15829/1560-4071-2025-6176
EDN: YFULAZ
Abstract
Aim. To assess the association of the allele and genotype frequencies of following single nucleotide polymorphisms: rs1801282 of the peroxisome proliferator-activated receptor gamma (PPARG) gene, rs5186 of the angiotensin II receptor type 1 (AGTR1) gene, rs699947 of the vascular endothelial growth factor A (VEGF-A) gene in patients with various phenotypes of abdominal (AO) and ectopic (EO) obesity.
Material and methods. The cross-sectional study included 100 Caucasian patients (47 men, 53 women, median age 58,5 [50;69] years). All patients underwent chest and retroperitoneal computed tomography with calculation of the volumes of perivascular (PVAT) and pericardial (PAT) adipose tissue, and perirenal fat thickness (PFT). PAT volume ≥3,2 cm3, PVAT volume ≥0,4 cm3, PFT thickness ≥1,91 cm were considered criteria for pericardial (PCO), perivascular (PVO) and perirenal (PRO) obesity. Alleles and genotypes of polymorphic markers of candidate genes were identified in all patients.
Results. In the distribution of genotypes of the polymorphic marker AGTR1 rs5186, statistical significance (p=0,014) was found between the group with any type of obesity and patients without obesity; the distribution of genotypes differed from the Hardy-Weinberg equilibrium (HWE) in the EO (p=0,0009) and mixed obesity (p=0,05) groups. With regard to the marker VEGF-A rs699947, a significant increase in the frequency of the mutant allele C (62,5%, 50%, 46,3%, 47,75%, respectively) was found in the EO, AO, and EO+AO groups with any type of obesity compared to the non-obese group (40%) (χ2=10,806; p=0,013). A deviation of the frequency of VEGF-A rs699947 genotypes from HWE was found in the EO group (p=0).
Conclusion. Our data suggest that single nucleotide polymorphisms PPARG rs1801282, AGTR1 rs5186, VEGF-A rs699947 may be associated with fat distribution in the body and be markers of various EO and AO phenotypes. Verification of our hypothesis requires additional studies with the inclusion of larger samples and comparison groups.
About the Authors
A. E. BraginaRussian Federation
Moscow
Competing Interests:
нет
M. K. Vasilchenko
Russian Federation
Moscow
Competing Interests:
нет
Yu. N. Rodionova
Russian Federation
Moscow
Competing Interests:
нет
K. K. Osadchiy
Russian Federation
Moscow
Competing Interests:
нет
A. P. Muravlev
Russian Federation
Moscow
Competing Interests:
нет
M. A. Voronkov
Russian Federation
Moscow
Competing Interests:
нет
E. A. Aleksandrova
Russian Federation
Moscow
Competing Interests:
нет
V. I. Podzolkov
Russian Federation
Moscow
Competing Interests:
нет
References
1. Balanova YuA, Shalnova SA, Deev AD, et al. Obesity in Russian population — prevalence and association with the non-communicable diseases risk factors. Russian Journal of Cardiology. 2018;(6):123-30. (In Russ.) doi: 10.15829/1560-4071-2018-6-123-130.
2. Neeland IJ, Ross R, Després JP, et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. The Lancet Diabetes & Endocrinology. 2019; 7(9):715-25. doi: 10.1016/S2213-8587(19)30084-1.
3. Thanassoulis G, Massaro JM, Hoffmann U, et al. Prevalence, Distribution, and Risk Factor Correlates of High Pericardial and Intrathoracic Fat Depots in the Framingham Heart Study. Circ: Cardiovascular Imaging. 2010;3(5):559-66. doi: 10.1161/CIRCIMAGING.110.956706.
4. Podzolkov VI, Bragina AE, Osadchiy KK, et al. Ectopic obesity in patients without manifested cardiovascular disease: regulations, frequency and clinical characteristics. Terapevticheskii arkhiv. 2022;94(9):1072-7. (In Russ.) doi: 10.26442/00403660.2022.09.201847.
5. Podzolkov VI, Bragina AE, Rodionova YuN, et al. Ectopic adipose tissue: frequency and clinical characteristics of obesity phenotypes in patients. Cardiovascular Therapy and Prevention. 2024;23(6):3980. (In Russ.) doi: 10.15829/1728-8800-2024-3980.
6. Sun C, Kovacs P, Guiu-Jurado E. Genetics of Body Fat Distribution: Comparative Analyses in Populations with European, Asian and African Ancestries. Genes. 2021;12(6):841. doi: 10.3390/genes12060841.
7. Agrawal S, Wang M, Klarqvist MDR, et al. Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots. Nat Commun. 2022;13(1):3771. doi: 10.1038/s41467-022-30931-2.
8. Panteleeva AA, Razgildina ND, Pobozheva IA, et al. Expression of Genes Encoding Nuclear Factors PPARγ, LXRβ, and RORα in Epicardial and Subcutaneous Adipose Tissues in Patients with Coronary Heart Disease. Bull Exp Biol Med. 2021;170(5):654-7. doi: 10.1007/s10517-021-05126-2.
9. Heid IM, Jackson AU, Randall JC, et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet. 2010;42(11):949-60. doi: 10.1038/ng.685.
10. Elkina AYu, Akimova NS, Shvarts Yu G. Polymorphism of ACE, AGT, AGTR1 genes as genetic predictors of hypertension. Russian Journal of Cardiology. 2021;26(1S):4143. (In Russ.) doi: 10.15829/1560-4071-2021-4143.
11. Adiyeva M, Aukenov N, Nurzhanova A, et al. The effect of AGTR1, AGТ, LPL, ADRB2 gene polymorphisms on central obesity in adolescents of the Kazakh population. BLL. 2022;124(01):53-8. doi: 10.4149/BLL_2023_008.
12. Dedov II, Mokrysheva NG, Mel'nichenko GA, et al. Obesity. Clinical guidelines. Consilium Medicum. 2021;23(4):311-25. (In Russ.) doi: 10.26442/20751753.2021.4.200832.
13. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39(33):3021-104. doi: 10.1093/EURHEARTJ/EHY339.
14. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111-88. doi: 10.1093/EURHEARTJ/EHZ455.
15. Dedov II, Shestakova MV, Mayorov AY, et al. Diabetes mellitus type 2 in adults. Diabetes mellitus. 2020;23(2S):4-102. (In Russ) doi: 10.14341/DM12507-9653.
16. Goldenberg L, Saliba W, Hayeq H, et al. The impact of abdominal fat on abdominal aorta calcification measured on non-enhanced CT. Medicine. 2018;97(49). doi: 10.1097/MD.0000000000013233.
17. Podzolkov VI, Bragina AE, Osadchiy KK, et al. Pararenal Fat Tissue: Rate of Pararenal Obesity and Relation with Anthropometric Indices of Obesity. Rational Pharmacotherapy in Cardiology. 2022;18(5):516-21. (In Russ.) doi: 10.20996/1819-6446-2022-09-04.
18. Drapkina OM, Imaeva AE, Kutsenko VA, et al. Dyslipidemia in the Russian Federation: population data, associations with risk factors. Cardiovascular Therapy and Prevention. 2023;22(8S):3791. (In Russ.) doi: 10.15829/1728-8800-2023-3791.
19. Khasanova KB, Medvedeva MS, Valeeva EV, et al. The role of the rs1801282 PPARG polymorphic marker in the prediction and choice of carbohydrate metabolism disorders management: A review. Consilium Medicum. 2022;24(4):266-70. (In Russ.) doi: 10.26442/20751753.2022.4.201672.
20. Sarhangi N, Sharifi F, Hashemian L, et al. PPARG (Pro12Ala) genetic variant and risk ofT2DM: a systematic review and meta-analysis. Sci Rep. 2020;10(1):12764. doi: 10.1038/s41598-020-69363-7.
21. Li S, He C, Nie H, et al. G Allele of the rs1801282 Polymorphism in PPARγ Gene Confers an Increased Risk of Obesity and Hypercholesterolemia, While T Allele of the rs3856806 Polymorphism Displays a Protective Role Against Dyslipidemia: A Systematic Review and Meta-Analysis. Front Endocrinol. 2022;13:919087. doi: 10.3389/fendo.2022.919087.
22. Bezmenova IN, Averyanova IV. 1166A>C polymorphism of the AGTR1 gene as a marker metabolic disorders in the North residents. Obes metabol. 2024;20(4):330-7. (In Russ.) doi: 10.14341/omet12986.
23. Razbekova M, Issanov A, Chan MY, et al. Genetic factors associated with obesity risks in a Kazakhstani population. BMJNPH. 2021;4(1):90-101. doi: 10.1136/bmjnph-2020-000139.
24. Procopciuc LM, Sitar-Tăut A, Pop D, et al. Renin angiotensin system polymorphisms in patients with metabolic syndrome (MetS). European Journal of Internal Medicine. 2010;21(5):414-8. doi: 10.1016/j.ejim.2010.06.001.
25. Semianiv M, Sydorchuk L, Semianiv I, et al. Dyslipidemia as a predictor of essential arterial hypertension depending on AGTR1 (RS5186) and VDR (RS2228570) genes polymorphism. 2022;29(2). Romanian Journal of Diabetes Nutrition and Metabolic Diseases. 2022;29(2):253-60.
26. Musso G, Saba F, Cassader M, et al. Angiotensin II Type 1 Receptor rs5186 Gene Variant Predicts Incident NAFLD and Associated Hypertension: Role of Dietary Fat-Induced ProInflammatory Cell Activation. Am J Gastroenterol. 2019;114(4):607-19. doi: 10.14309/ajg.0000000000000154.
27. Hsiao PJ, Lu MY, Chiang FY, et al. Vascular endothelial growth factor gene polymorphisms in thyroid cancer. Journal of Endocrinology. 2007;195(2):265-70. doi: 10.1677/JOE-07-0395.
28. Skrypnik D, Mostowska A, Jagodziński P, et al. Association of rs699947 (-2578 C/A) and rs2010963 (-634 G/C) Single Nucleotide Polymorphisms of the VEGF Gene, VEGF-A and Leptin Serum Level, and Cardiovascular Risk in Patients with Excess Body Mass: A Case— Control Study. JCM. 2020;9(2):469. doi: 10.3390/jcm9020469.
Supplementary files
What is already known about the subject?
- Ectopic fat depots are not always associated with obesity in general; this dissociation makes studying the distribution of adipose tissue interesting, as well as the influence of genetic/epigenetic factors on this process.
- Many genes and polymorphisms have been identified that are of interest in relation to obesity phenotypes and the distribution of adipose tissue, among them there are genes such as PPARG, VEGF-Aand AGTR1.
What might this study add?
- A following significant difference in the genotype distribution of AGTR1rs5186 polymorphism was found in individuals with any type of obesity compared to patients without obesity: individuals with any type of obesity had a higher frequency of the mutant allele C.
- The distribution of genotypes and the increase in the frequency of the mutant allele C of AGTR1rs5186 polymorphism in groups with isolated EO and mixed obesity (EO+AO), as well as the distribution of alleles and the increase in the frequency of the mutant allele C of VEGF-Ars699947 polymorphism in the group with isolated EO differ from the general population, which is manifested by a deviation from the HWE; this suggests that these single nucleotide polymorphisms can be markers of obesity.
Review
For citations:
Bragina A.E., Vasilchenko M.K., Rodionova Yu.N., Osadchiy K.K., Muravlev A.P., Voronkov M.A., Aleksandrova E.A., Podzolkov V.I. Polymorphism of the PPARG, AGTR1, VEGF-A genes: frequency and association with obesity phenotypes. Russian Journal of Cardiology. 2025;30(3):6176. (In Russ.) https://doi.org/10.15829/1560-4071-2025-6176. EDN: YFULAZ