Abstract
Introduction
Obesity is the result of a complex interaction between multiple genetic traits and psychological, behavioral, nutritional and environmental factors.
Objectives
The aims of the study were (a) to comparatively evaluate the presence of 20 candidate gene single nucleotide polymorphisms (SNPs) in morbidly obese patients, (2) their association to comorbid conditions and (3) their impact on weight loss after a Roux-en-Y gastric bypass (RYGB).
Patients and Methods
Two hundred forty-nine patients were eligible for this study. Clinical, anthropometric, biochemical and demographic variables were analyzed. Body mass index (BMI) and composition were assessed by bioelectrical impedance. Twenty SNPs were included for analysis.
Results
There were 168 Mexican mestizos (67.5 %) and 81 (32.5 %) patients with other ancestral origin. One hundred fifty-nine (64.1 %) were females. Mean ± SD age of the general cohort was 41.1 ± 11.3 years (17–71). Preoperative mean ± SD BMI was 42.5 ± 6.5 kg/m2. There were no significant differences between mestizo and non-mestizo for most SNPs except for IFI, LIPC, and ST8SIA2. FTO (OR = 1.71; CI95 % = 1.14–2.57; p = 0.008) and APOB (OR = 0.31; CI95 % = 0.14–0.72; p = 0.004) result is statistically associated to high blood pressure and FTO (OR = 2.0; CI95 % = 1.3–3.1; p = 0.001), GNB3 (OR = 2.69; CI95 % = 1.0–7.2; p = 0.04), IFI30 (OR = 2.0; CI95 % = 1.16–3.6; p = 0.01), and MC4R (OR = 1.81; CI95 % = 1.13–2.9; p = 0.01) to type 2 diabetes (T2D). Based on ANOVA analysis, POMC (rs1042571) was the SNP most significantly associated to a higher weight loss after RYGB.
Conclusions
Obese patients have similar SNP frequencies. Several SNP results are statistically associated to high blood pressure and T2D. POMC was significantly associated to a higher surgically induced weight loss.
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References
Barrera-Cruz A, Rodriguez-Gonzalez A, Molina-Ayala MA. The current state of obesity in Mexico. Rev Med Inst Mex Seguro Soc. 2013;51(3):292–9.
[ENSANUT 2012: Analysis of its main results]. Salud Publica Mex. 2013;55 Suppl 2:S81–2.
Ponce-Garcia I, Simarro-Rueda M, Carbayo-Herencia JA, et al. Prognostic value of obesity on both overall mortality and cardiovascular disease in the general population. PLoS One. 2015;10(5):e0127369.
Colombo MG, Meisinger C, Amann U, et al. Association of obesity and long-term mortality in patients with acute myocardial infarction with and without diabetes mellitus: results from the MONICA/KORA myocardial infarction registry. Cardiovasc Diabetol. 2015;14:24.
Puzziferri N, Roshek 3rd TB, Mayo HG, et al. Long-term follow-up after bariatric surgery: a systematic review. JAMA. 2014;312(9):934–42.
Brethauer SA, Kothari S, Sudan R, et al. Systematic review on reoperative bariatric surgery: American Society for Metabolic and Bariatric Surgery Revision Task Force. Surg Obes Relat Dis. 2014;10(5):952–72.
Cooper TC, Simmons EB, Webb K, Burns JL, Kushner RF. Trends in weight regain following Roux-en-Y gastric bypass (RYGB) bariatric surgery. Obes Surg. 2015.
Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197–206.
Sarzynski MA, Jacobson P, Rankinen T, et al. Association of GWAS-based candidate genes with HDL-cholesterol levels before and after bariatric surgery in the Swedish obese subjects study. J Clin Endocrinol Metab. 2011;96(6):E953–7.
Sarzynski MA, Jacobson P, Rankinen T, et al. Associations of markers in 11 obesity candidate genes with maximal weight loss and weight regain in the SOS bariatric surgery cases. Int J Obes. 2011;35(5):676–83.
Liu CT, Buchkovich ML, Winkler TW, et al. Multi-ethnic fine-mapping of 14 central adiposity loci. Hum Mol Genet. 2014;23(17):4738–44.
Surakka I, Horikoshi M, Magi R, et al. The impact of low-frequency and rare variants on lipid levels. Nat Genet. 2015;47(6):589–97.
Wang X, Strizich G, Hu Y, Wang T, Kaplan RC, Qi Q. Genetic markers of type 2 diabetes: progress in genome-wide association studies and clinical application for risk prediction. J Diabetes. 2015.
Setoh K, Terao C, Muro S, et al. Three missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels. Nat Commun. 2015;6:7754.
Winkler TW, Justice AE, Graff M, et al. The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study. PLoS Genet. 2015;11(10):e1005378.
Hagg S, Ganna A, Van Der Laan SW, Esko T, Pers TH, Locke AE, et al. Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity. Hum Mol Genet. 2015.
Robinson MR, Hemani G, Medina-Gomez C, Mezzavilla M, Esko T, Shakhbazov K, et al. Population genetic differentiation of height and body mass index across Europe. Nat Genet. 2015.
Silva-Zolezzi I, Hidalgo-Miranda A, Estrada-Gil J, et al. Analysis of genomic diversity in Mexican mestizo populations to develop genomic medicine in Mexico. Proc Natl Acad Sci U S A. 2009;106(21):8611–6.
Karastergiou K. The interplay between sex, ethnicity, and adipose tissue characteristics. Curr Obes Rep. 2015;4(2):269–78.
Baldridge AS, Pacheco JA, Aufox SA, et al. Factors associated with long-term weight loss following bariatric surgery using 2 methods for repeated measures analysis. Am J Epidemiol. 2015;182(3):235–43.
Basile KJ, Johnson ME, Xia Q, et al. Genetic susceptibility to type 2 diabetes and obesity: follow-up of findings from genome-wide association studies. Int J Endocrinol. 2014;2014:769671.
Claussnitzer M, Dankel SN, Kim KH, et al. FTO obesity variant circuitry and adipocyte browning in humans. N Engl J Med. 2015;373(10):895–907.
Chakravartty S, Tassinari D, Salerno A, et al. What is the mechanism behind weight loss maintenance with gastric bypass? Curr Obes Rep. 2015;4(2):262–8.
Wroblewski E, Swidnicka-Siergiejko A, Hady HR, et al. Variation in blood levels of hormones in obese patients following weight reduction induced by endoscopic and surgical bariatric therapies. Cytokine. 2016;77:56–62.
Malin SK, Kashyap SR. Differences in weight loss and gut hormones: Rouen-Y gastric bypass and sleeve gastrectomy surgery. Curr Obes Rep. 2015;4(2):279–86.
Brandao I, Ramalho S, Pinto-Bastos A, et al. Metabolic profile and psychological variables after bariatric surgery: association with weight outcomes. Eat Weight Disord. 2015;20(4):513–8.
Rodrigues GK, Resende CM, Durso DF, et al. A single FTO gene variant rs9939609 is associated with body weight evolution in a multiethnic extremely obese population that underwent bariatric surgery. Nutrition. 2015;31(11–12):1344–50.
Chen HH, Lee WJ, Wang W, et al. Ala55Val polymorphism on UCP2 gene predicts greater weight loss in morbidly obese patients undergoing gastric banding. Obes Surg. 2007;17(7):926–33.
Poitou C, Lacorte JM, Coupaye M, et al. Relationship between single nucleotide polymorphisms in leptin, IL6 and adiponectin genes and their circulating product in morbidly obese subjects before and after gastric banding surgery. Obes Surg. 2005;15(1):11–23.
Dominguez-Reyes T, Astudillo-Lopez CC, Salgado-Goytia L, et al. Interaction of dietary fat intake with APOA2, APOA5 and LEPR polymorphisms and its relationship with obesity and dyslipidemia in young subjects. Lipids Health Dis. 2015;14(1):106.
Culnan DM, Cooney RN, Stanley B, et al. Apolipoprotein A-IV, a putative satiety/antiatherogenic factor, rises after gastric bypass. Obesity (Silver Spring). 2009;17(1):46–52.
Gantz I, Fong TM. The melanocortin system. Am J Physiol Endocrinol Metab. 2003;284(3):E468–74.
Mirshahi UL, Still CD, Masker KK, et al. The MC4R(I251L) allele is associated with better metabolic status and more weight loss after gastric bypass surgery. J Clin Endocrinol Metab. 2011;96(12):E2088–96.
Jelin EB, Daggag H, Speer AL, Hameed N, Lessan N, Barakat M, et al. Melanocortin-4 receptor signaling is not required for short-term weight loss after sleeve gastrectomy in pediatric patients. Int J Obes (Lond). 2015.
Hatoum IJ, Stylopoulos N, Vanhoose AM, et al. Melanocortin-4 receptor signaling is required for weight loss after gastric bypass surgery. J Clin Endocrinol Metab. 2012;97(6):E1023–31.
Aslan IR, Campos GM, Calton MA, et al. Weight loss after Roux-en-Y gastric bypass in obese patients heterozygous for MC4R mutations. Obes Surg. 2011;21(7):930–4.
Rasmussen-Torvik LJ, Baldridge AS, Pacheco JA, et al. rs4771122 predicts multiple measures of long-term weight loss after bariatric surgery. Obes Surg. 2015;25(11):2225–9.
Adams ST, Salhab M, Hussain ZI, et al. Roux-en-Y gastric bypass for morbid obesity: what are the preoperative predictors of weight loss? Postgrad Med J. 2013;89(1053):411–6. quiz 5, 6
Coleman KJ, Brookey J. Gender and racial/ethnic background predict weight loss after Roux-en-Y gastric bypass independent of health and lifestyle behaviors. Obes Surg. 2014;24(10):1729–36.
Livhits M, Mercado C, Yermilov I, et al. Preoperative predictors of weight loss following bariatric surgery: systematic review. Obes Surg. 2012;22(1):70–89.
Acknowledgements
We would like to express our gratitude to all the members of our clinic (CNOAM) for their commitment and support on this project.
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This project was supported by a research grant from Johnson & Johnson Medical Mexico.
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The manuscript has been read and approved by all authors. All the authors declare that they have no potential conflicts of interest.
Ethical Statement
This protocol was approved by our institutional research committee in humans and followed the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Consent Statement
Informed consent was obtained from all individual participants included in this study. All informed consent sheets were signed, properly filed, and saved. Samples and clinical data were unidentified for anonymity rights.
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Velázquez-Fernández, D., Mercado-Celis, G., Flores-Morales, J. et al. Analysis of Gene Candidate SNP and Ancestral Origin Associated to Obesity and Postoperative Weight Loss in a Cohort of Obese Patients Undergoing RYGB. OBES SURG 27, 1481–1492 (2017). https://doi.org/10.1007/s11695-016-2501-9
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DOI: https://doi.org/10.1007/s11695-016-2501-9