Association between rs571312 MC4R and rs3810291 TMEM160 single-nucleotide polymorphisms and metabolic surgery outcomes
DOI:
https://doi.org/10.30978/GS-2025-3-29Keywords:
treatment, excess weight loss, gene, polymorphismsAbstract
Objective – to determine the association between the SNP rs571312 MC4R and SNP rs3810291 TMEM160 genes and the results of metabolic surgery.
Materials and methods. A prospective, observational, monocentric cohort study was conducted at the Department of General Surgery No2 of Bogomolets National Medical University. A total of 112 patients with surgical indications were offered bariatric surgery. Patients who agreed to undergo bariatric surgery (n=53) comprised the main group. Those who refused surgical treatment (n=59) formed the control group. The main group underwent bariatric interventions, including laparoscopic gastric bypass and laparoscopic sleeve gastrectomy, whereas patients with BMI ≥50 kg/m2 had a twostage surgical treatment involving intragastric balloon placement for a period of 6 months, followed by gastric bypass within 14 days after balloon removal. The results for both groups were evaluated one year after the start of treatment. In the control group, 59 patients suffering from obesity received conservative treatment. Before the start of treatment, all patients underwent anthropometric examinations and analysis of buccal epithelial scrapings. Genetic studies included DNA collection and isolation, as well as genotyping to determine polymorphisms of the rs571312 MC4R and rs3810291 TMEM160 genes.
Results. A strong correlation was found between bariatric surgery outcomes and the presence of rs571312 MC4R and rs3810291 TMEM160 gene polymorphisms in the study group (r=0.622; p≥0.001). There was no significant association between the degree of gene dominance and bariatric surgery outcomes (r=0.112, p≥0.5).
Conclusions. In the studied cohort, a relationship was found between the effectiveness of bariatric procedures and the presence of the rs571312 MC4R (r=0.465) and rs3810291 TMEM160 (r=0.55) polymorphisms, as well as the concurrent presence of both polymorphisms (r=0.622). The detection of these polymorphisms is associated with bariatric surgery outcomes, regardless of the degree of their genetic dominance (r=0.467).
References
AbouHashem N, Zaied RE, Al-Shafai K, Nofal M, Syed N, Al-Shafai M. The Spectrum of Genetic Variants Associated with the Development of Monogenic Obesity in Qatar. Obes Facts. 2022;15(3):357-365. http://doi.org/10.1159/000521851. Epub 2022 Jan 13. PMID: 35026759; PMCID: PMC9210005.
Al-Humadi AW, Alabduljabbar K, Alsaqaaby MS, Talaee H, le Roux CW. Obesity Characteristics Are Poor Predictors of Genetic Mutations Associated with Obesity. J Clin Med. 2023 Oct 7;12(19):6396. http://doi.org/10.3390/jcm12196396. PMID: 37835041; PMCID: PMC10573901.
Bandstein M, Voisin S, Nilsson EK, Schultes B, Ernst B, Thurnheer M, Benedict C, Mwinyi J, Schiöth HB. A Genetic Risk Score Is Associated with Weight Loss Following Roux-en Y Gastric Bypass Surgery. Obes Surg. 2016 Sep;26(9):2183-2189. http://doi.org/10.1007/s11695-016-2072-9. PMID: 26832135; PMCID: PMC4985537.
Bouchard C. Genetics of Obesity: What We Have Learned Over Decades of Research. Obesity (Silver Spring). 2021 May;29(5):802-820. http://doi.org/10.1002/oby.23116. PMID: 33899337.
Clément K, van den Akker E, Argente J, Bahm A, Chung WK, Connors H, De Waele K, Farooqi IS, Gonneau-Lejeune J, Gordon G, Kohlsdorf K, Poitou C, Puder L, Swain J, Stewart M, Yuan G, Wabitsch M, Kühnen P; Setmelanotide POMC and LEPR Phase 3 Trial Investigators. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol. 2020 Dec;8(12):960-970. http://doi.org/10.1016/S2213-8587(20)30364-8. Epub 2020 Oct 30. PMID: 33137293.
Courbage S, Poitou C, Le Beyec-Le Bihan J, Karsenty A, Lemale J, Pelloux V, Lacorte JM, Carel JC, Lecomte N, Storey C, De Filippo G, Coupaye M, Oppert JM, Tounian P, Clément K, Dubern B. Implication of Heterozygous Variants in Genes of the Leptin-Melanocortin Pathway in Severe Obesity. J Clin Endocrinol Metab. 2021 Sep 27;106(10):2991-3006. http://doi.org/10.1210/clinem/dgab404. PMID: 34097736.
Folon L, Baron M, Toussaint B, Vaillant E, Boissel M, Scherrer V, Loiselle H, Leloire A, Badreddine A, Balkau B, Charpentier G, Franc S, Marre M, Aboulouard S, Salzet M, Canouil M, Derhourhi M, Froguel P, Bonnefond A. Contribution of heterozygous PCSK1 variants to obesity and implications for precision medicine: a case-control study. Lancet Diabetes Endocrinol. 2023 Mar;11(3):182-190. http://doi.org/10.1016/S2213-8587(22)00392-8. PMID: 36822744.
Ioffe OY, Molnar IM, Tsyura YP, et al. Optimal timing for radical bariatric operations after removal of intragastric balloon Actual Problems of the Modern Medicine:Bulletin of Ukrainian Medical Stomatological Academy. 2017;17(3):115-118. Ukrainian.
Liu L, Pei YF, Liu TL, Hu WZ, Yang XL, Li SC, Hai R, Ran S, Zhao LJ, Shen H, Tian Q, Xiao HM, Zhang K, Deng HW, Zhang L. Identification of a 1p21 independent functional variant for abdominal obesity. Int J Obes (Lond). 2019 Dec;43(12):2480-2490. http://doi.org/10.1038/s41366-019-0350-z. Epub 2019 Apr 3. PMID: 30944420; PMCID: PMC6776704.
Loos RJF, Yeo GSH. The genetics of obesity: from discovery to biology. Nat Rev Genet. 2022 Feb;23(2):120-133. http://doi.org/10.1038/s41576-021-00414-z. Epub 2021 Sep 23. PMID: 34556834; PMCID: PMC8459824.
Lutz SZ, Falcenberg M, Machicao F, Peter A, Kächele M, Randrianarisoa E, Lehn-Stefan A, Wagner R, Machann J, Schick F, Heni M, Ullrich A, Fritsche A, Stefan N, Häring HU, Staiger H, Kantartzis K. Single Nucleotide Polymorphisms in the G-Protein Coupled Receptor Kinase 5 (GRK5) Gene are associated with Plasma LDL-Cholesterol Levels in Humans. Sci Rep. 2018 May 17;8(1):7745. http://doi.org/10.1038/s41598-018-26055-7. PMID: 29773828; PMCID: PMC5958094.
Ng MC, Tam CH, So WY, Ho JS, Chan AW, Lee HM, Wang Y, Lam VK, Chan JC, Ma RC. Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. J Clin Endocrinol Metab. 2010 May;95(5):2418-25. http://doi.org/10.1210/jc.2009-2077. Epub 2010 Mar 9. PMID: 20215397.
Olateju IV, Ogwu D, Owolabi MO, Azode U, Osula F, Okeke R, Akabalu I. Role of Behavioral Interventions in the Management of Obesity. Cureus. 2021 Sep 18;13(9):e18080. http://doi.org/10.7759/cureus.18080. PMID: 34671541; PMCID: PMC8522530.
Okati-Aliabad H, Ansari-Moghaddam A, Kargar S, Jabbari N. Prevalence of Obesity and Overweight among Adults in the Middle East Countries from 2000 to 2020: A Systematic Review and Meta-Analysis. J Obes. 2022 Feb 3;2022:8074837. http://doi.org/10.1155/2022/8074837. PMID: 35154826; PMCID: PMC8831052.
Thanos PK, Hanna C, Mihalkovic A, Hoffman A, Posner A, Butsch J, Blum K, Georger L, Mastrandrea LD, Quattrin T. Genetic Correlates as a Predictor of Bariatric Surgery Outcomes after 1 Year. Biomedicines. 2023 Sep 27;11(10):2644. http://doi.org/10.3390/biomedicines11102644. PMID: 37893019; PMCID: PMC10603884.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Authors
This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.
