Abstract
Purpose:
To test whether DNA sequence variation in 11 obesity genes is associated with maximum weight loss and weight regain over 6 years of follow-up in bariatric surgery patients of the Swedish obese subjects (SOS) intervention study.
Methods:
A total of 1443 subjects were available for analysis (vertical banded gastroplasty: n=966, banding: n=293 and gastric bypass: n=184). Single-nucleotide polymorphisms (SNPs) from the following 11 genes were included: ADIPOQ, BDNF, FTO, GNB3, LEP, LEPR, MC4R, NR3C1, PPARG, PPARGC1A and TNF. General linear models were used to analyze associations between the SNPs and maximum weight loss and weight regain.
Results:
The average maximum weight loss was 33.7 kg (s.d. 13.3; min −95.5 kg, max +2.0 kg), which was reached 2.2 (s.d. 1.6) years after the surgery. Subjects regained approximately 12 kg (range 0.0–51.4 kg) by year 6. After correcting for multiple testing, the FTO SNP rs16945088 remained significantly associated with maximum weight loss (P=0.0002), as minor allele carriers lost approximately 3 kg less compared with common allele homozygotes. This association was particularly evident in the banding surgery patients (P<0.0001), whereas no significant association was found in the gastric bypass subjects. No other SNPs were associated with maximum weight loss. Furthermore, no SNPs were significantly associated with weight regain.
Conclusion:
The FTO SNP rs16945088 was associated with maximum weight loss after banding surgery. We found no evidence that obesity-risk SNPs in FTO or other obesity candidate genes derived from genome-wide association studies are associated with maximum weight loss or weight regain over 6 years of follow-up in bariatric surgery patients. The potential role of other obesity genes remains to be investigated.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
WHO. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: 1–253.
Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 357: 741–752.
Deitel M . Overview of operations for morbid obesity. World J Surg 1998; 22: 913–918.
Sjostrom L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351: 2683–2693.
Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD et al. Long-term mortality after gastric bypass surgery. N Engl J Med 2007; 357: 753–761.
Sjostrom L, Gummesson A, Sjostrom CD, Narbro K, Peltonen M, Wedel H et al. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol 2009; 10: 653–662.
Hsu LK, Benotti PN, Dwyer J, Roberts SB, Saltzman E, Shikora S et al. Nonsurgical factors that influence the outcome of bariatric surgery: a review. Psychosom Med 1998; 60: 338–346.
Lancaster K, Burgard M, Howell L, Krahn D, Crosby R, Wonderlich S et al. Long-term follow-up of patients’ status after gastric bypass. Obes Surg 2001; 11: 464–468.
Bouchard C, Tremblay A, Despres JP, Theriault G, Nadeau A, Lupien PJ et al. The response to exercise with constant energy intake in identical twins. Obes Res 1994; 2: 400–410.
Hainer V, Stunkard AJ, Kunesová M, Parízková J, Stich V, Allison DB . Intrapair resemblance in very low calorie diet-induced weight loss in female obese identical twins. Int J Obes Relat Metab Disord 2000; 24: 1051–1057.
Hofker M, Wijmenga C . A supersized list of obesity genes. Nat Genet 2009; 41: 139–140.
Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 2006; 14: 529–644.
Sjostrom L, Larsson B, Backman L, Bengtsson C, Bouchard C, Dahlgren S et al. Swedish obese subjects (SOS). Recruitment for an intervention study and a selected description of the obese state. Int J Obes Relat Metab Disord 1992; 16: 465–479.
International HapMap Consortium. The International HapMap Project. Nature 2003; 426: 789–796.
de Bakker PI, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D . Efficiency and power in genetic association studies. Nat Genet 2005; 37: 1217–1223.
Abecasis GR, Cookson WOC . GOLD--Graphical Overview of Linkage Disequilibrium. Bioinformatics 2000; 16: 182–183.
Nyholt DR . A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 2004; 74: 765–769.
Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM 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: 889–894.
Rankinen T, Rice T, Teran-Garcia M, Rao DC, Bouchard C . FTO genotype is associated with exercise training-induced changes in body composition. Obesity (Silver Spring) 2010; 18: 322–326.
Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 2008; 40: 768–775.
Meyre D, Delplanque J, Chevre JC, Lecoeur C, Lobbens S, Gallina S et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 2009; 41: 157–159.
Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009; 41: 18–24.
Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41: 25–34.
Haupt A, Thamer C, Machann J, Kirchhoff K, Stefan N, Tschritter O et al. Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss. Obesity (Silver Spring) 2008; 16: 1969–1972.
Lappalainen TJ, Tolppanen AM, Kolehmainen M, Schwab U, Lindstrom J, Tuomilehto J et al. The common variant in the FTO gene did not modify the effect of lifestyle changes on body weight: the Finnish Diabetes Prevention Study. Obesity (Silver Spring) 2009; 17: 832–836.
Franks PW, Jablonski KA, Delahanty LM, McAteer JB, Kahn SE, Knowler WC et al. Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program. Diabetologia 2008; 51: 2214–2223.
Muller TD, Hinney A, Scherag A, Nguyen TT, Schreiner F, Schafer H et al. ‘Fat mass and obesity associated’ gene (FTO): no significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents. BMC Med Genet 2008; 9: 85.
Haupt A, Thamer C, Heni M, Tschritter O, Machann J, Schick F et al. Impact of variation near MC4R on whole-body fat distribution, liver fat, and weight loss. Obesity (Silver Spring) 2009; 17: 1942–1945.
Nicklas BJ, van Rossum EF, Berman DM, Ryan AS, Dennis KE, Shuldiner AR . Genetic variation in the peroxisome proliferator-activated receptor-gamma2 gene (Pro12Ala) affects metabolic responses to weight loss and subsequent weight regain. Diabetes 2001; 50: 2172–2176.
Lindi VI, Uusitupa MI, Lindstrom J, Louheranta A, Eriksson JG, Valle TT et al. Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes 2002; 51: 2581–2586.
Matsuo T, Nakata Y, Katayama Y, Iemitsu M, Maeda S, Okura T et al. PPARG genotype accounts for part of individual variation in body weight reduction in response to calorie restriction. Obesity (Silver Spring) 2009; 17: 1924–1931.
Zacharova J, Chiasson JL, Laakso M . Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance. Obes Res 2005; 13: 501–506.
Zacharova J, Chiasson JL, Laakso M . The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. Diabetes 2005; 54: 893–899.
Chapman AE, Kiroff G, Game P, Foster B, O’Brien P, Ham J et al. Laparoscopic adjustable gastric banding in the treatment of obesity: a systematic literature review. Surgery 2004; 135: 326–351.
Sesti G, Perego L, Cardellini M, Andreozzi F, Ricasoli C, Vedani P et al. Impact of common polymorphisms in candidate genes for insulin resistance and obesity on weight loss of morbidly obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet. J Clin Endocrinol Metab 2005; 90: 5064–5069.
Potoczna N, Branson R, Kral JG, Piec G, Steffen R, Ricklin T et al. Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesity. J Gastrointest Surg 2004; 8: 971–981.
Potoczna N, Wertli M, Steffen R, Ricklin T, Lentes KU, Horber FF . G protein polymorphisms do not predict weight loss and improvement of hypertension in severely obese patients. J Gastrointest Surg 2004; 8: 862–868.
Chen HH, Lee WJ, Wang W, Huang MT, Lee YC, Pan WH . Ala55Val polymorphism on UCP2 gene predicts greater weight loss in morbidly obese patients undergoing gastric banding. Obes Surg 2007; 17: 926–933.
Pontiroli AE, Pizzocri P, Librenti MC, Vedani P, Marchi M, Cucchi E et al. Laparoscopic adjustable gastric banding for the treatment of morbid (grade 3) obesity and its metabolic complications: a three-year study. J Clin Endocrinol Metab 2002; 87: 3555–3561.
Sugerman HJ, Starkey JV, Birkenhauer R . A randomized prospective trial of gastric bypass versus vertical banded gastroplasty for morbid obesity and their effects on sweets versus non-sweets eaters. Ann Surg 1987; 205: 613–624.
Acknowledgements
This work was supported by grants from the Coypu Foundation, the Swedish Research Council (K2010-55X-11285-13), the Swedish foundation for Strategic Research to Sahlgrenska Center for Cardiovascular and Metabolic Research, the Swedish Diabetes foundation and the Swedish federal government under the LUA/ALF agreement. C Bouchard is partially supported by the George A Bray Chair in Nutrition.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Supplementary Information accompanies the paper on International Journal of Obesity website
Supplementary information
Rights and permissions
About this article
Cite this article
Sarzynski, M., 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 35, 676–683 (2011). https://doi.org/10.1038/ijo.2010.166
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2010.166
Keywords
This article is cited by
-
High Prevalence of Positive Genetic Obesity Variants in Postoperative Bariatric Surgery Patients with Weight Regain Presenting for Medical Obesity Intervention
Obesity Surgery (2024)
-
How to address weight regain after bariatric surgery in an individualized way
Reviews in Endocrine and Metabolic Disorders (2023)
-
The Influence of Single Nucleotide Polymorphisms On Body Weight Trajectory After Bariatric Surgery: A Systematic Review
Current Obesity Reports (2023)
-
The joint effect of PPARG upstream genetic variation in association with long-term persistent obesity: Tehran cardio-metabolic genetic study (TCGS)
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity (2021)
-
A Systematic Review of Genetic Correlates of Weight Loss After Bariatric Surgery
Obesity Surgery (2021)