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A Genetic Variant in Proximity to the Gene LYPLAL1 Is Associated with Lower Hunger Feelings and Increased Weight Loss Following Roux-En-Y Gastric Bypass Surgery

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A Genetic Variant in Proximity to the Gene LYPLAL1 Is Associated with Lower Hunger Feelings and Increased Weight Loss Following Roux-En-Y Gastric Bypass Surgery Scandinavian Journal of Gastroenterology ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20 A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery Marcus Bandstein, Jessica Mwinyi, Barbara Ernst, Martin Thurnheer, Bernd Schultes & Helgi B. Schiöth To cite this article: Marcus Bandstein, Jessica Mwinyi, Barbara Ernst, Martin Thurnheer, Bernd Schultes & Helgi B. Schiöth (2016) A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery, Scandinavian Journal of Gastroenterology, 51:9, 1050-1055, DOI: 10.3109/00365521.2016.1166519 To link to this article: http://dx.doi.org/10.3109/00365521.2016.1166519 © 2016 The Author(s). Published by Informa View supplementary material UK Limited, trading as Taylor & Francis Group. Published online: 16 May 2016. Submit your article to this journal Article views: 154 View related articles View Crossmark data Citing articles: 1 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [Uppsala Universitetsbibliotek] Date: 06 October 2016, At: 00:18 SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 2016 VOL. 51, NO. 9, 1050–1055 http://dx.doi.org/10.3109/00365521.2016.1166519 A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery Marcus Bandsteina, Jessica Mwinyia, Barbara Ernstb, Martin Thurnheerb, Bernd Schultesb and Helgi B. Schioth€ a aDepartment of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden; bInterdisciplinary Obesity Center, eSwiss Medical & Surgical Center, St. Gallen, Switzerland ABSTRACT ARTICLE HISTORY Objective: Bariatric surgery is the most efficient treatment of severe obesity. We investigated to what Received 10 February 2016 extent BMI- or waist-hip ratio (WHR)-related genetic variants are associated with excess BMI loss (EBMIL) Revised 8 March 2016 two years after Roux-en-Y gastric bypass (RYGB) surgery, and elucidated the affected biological Accepted 8 March 2016 pathways. 2 KEYWORDS Methods: Two-hundred fifty-one obese patients (age: 43 ± 10.7, preoperative BMI: 45.1 ± 6.1 kg/m , 186 LYPLAL1; rs4846567; RYGB; women) underwent RYGB surgery and were followed up after two years with regard to BMI. Patients single nucleotide were genotyped for 32 single-nucleotide polymorphisms (SNPs) that were investigated with regard to polymorphism; Three Factor their impact on response to RYGB and preoperatively measured Three Factor Eating Questionnaire Eating Questionnaire (TFEQ) scores. Results: Homozygous T carriers of the SNP rs4846567 in proximity to the Lysophospholipase-like 1 (LYPLAL1) gene showed a 7% higher EBMIL compared to wild-type and heterozygous carriers (p ¼ 0.031). TT-allele carriers showed furthermore lower scores for Hunger (74%, p < 0.001), lower Disinhibition (53%, p < 0.001), and higher Cognitive restraint (21%, p ¼ 0.017) than GG/GT carriers in the TFEQ. Patients within the lowest quartile of Hunger scores had a 32% greater EBMIL compared to patients in the highest quartile (p < 0.001). Conclusion: The LYPLAL1 genotype is associated with differences in eating behavior and loss of exten- sive body weight following RYGB surgery. Genotyping and the use of eating behavior-related question- naires may help to estimate the RYGB-associated therapy success. Introduction changes in body weight and BMI.[9,10] Whether preopera- tively obtained eating behavior scores may be linked to the Obesity is of multifactorial pathogenesis, whereby genetic, magnitude of weight loss after bariatric surgery has not yet epigenetic and non-genetic factors appear to play a signifi- been proven.[2,3] cant role. Currently, the most efficient treatment option for Several phenotypes, such as age, surgery type and BMI severely obese patients is Roux-en-Y gastric bypass (RYGB) before surgery, have been identified to influence the success surgery. However, large interindividual differences in weight in weight loss after RYGB surgery.[11,12] A genetic influence loss are observed after RYGB surgery.[1] The reasons for this on the development of obesity and body fat distribution has observation are not yet fully elucidated. Psychological factors also been reported in both targeted and genome wide associ- related to eating behavior such as impulse control and hun- ation studies (GWAS).[13–16] Genetic variants detected in ger affect weight loss.[2,3] Dietary patterns and food prefer- these studies are located e.g., in the fat mass and obesity- ence are linked to obesity and body fat distribution in associated gene (FTO) and leptin, and have been found to be general and specifically to abdominal obesity.[4,5] The Three associated with eating behavior.[17,18] The mechanisms by Factor Eating Questionnaire (TFEQ) is a tool to assess individ- which such variants may influence the risk for obesity are ual eating habits by evaluating three traits: Hunger, largely unknown. Disinhibition, and Cognitive restraint.[6,7] Several studies indi- Hitherto, studies investigated separately the impact of cate that the TFEQ is a useful instrument to explain changes preoperative eating behavior and the influence of genetic in body weight based on food intake behavior. Using the risk variants on therapy success in bariatric surgery. Studies TFEQ, French et al. detected an association between BMI and investigating the interaction of all these three parameters Hunger and Disinhibition,[8] while others were able to show have not yet been published. In the current study, we that changes in Cognitive restraint are associated with investigate to what extent eating behavior, as quantified by CONTACT Marcus Bandstein [email protected] Department of Neuroscience, Uppsala University, Box 593, 751 24 Uppsala, Sweden Supplemental data for this article can be accessed here. ß 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 1051 the TFEQ, has an impact on excess BMI loss (EBMIL) after The TFEQ RYGB bariatric surgery, and if BMI and waist-hip ratio The original version of the Three Factor Eating Questionnaire (WHR)-associated genetic variants may have the ability to was used to assess eating behavior prior to RYGB surgery. influence eating behavior. The TFEQ comprises 51 questions, which measure three dimensions of eating behavior: Hunger (14 questions), Materials and methods Disinhibition (16 questions), and Cognitive restraint (21 ques- tions). Each question is dichotomously evaluated (score 0 or Patients 1). Scores are subsequently summed up to a final score for each of the three categories leading to maximum reachable Two-hundred and fifty-one obese patients, as defined by points of 14, 16, and 21, respectively. BMI >30kg/m2, were included in the study (mean ± SD; age: 43.0 ± 10.7 years, preoperative BMI: 45.1 ± 6.1 kg/m2, 186 women). All participants underwent RYGB surgery at the Genotyping Interdisciplinary Obesity Center, St. Gallen, Switzerland. Study participants completed the TFEQ-51 questionnaire at the Two-hundred thirt-seven patients of the RYGB cohort were study center, after an over-night fast, in the morning before genotyped for 32 single-nucleotide polymorphisms (SNPs) the surgical intervention. Two different variants of RYGB sur- that have been earlier associated with larger BMI or WHR in gery were performed: proximal and distal RYGB. In both pro- two comprehensive GWA studies. Only SNPs with a reported cedures, the largest part of the stomach was transected, and minor allele frequency of at least 15% were taken into consid- a small gastric pouch of about 20–30 ml was anatomized to eration.[13,14] Genotyping was performed using the Illumina the proximal jejunum with the diameter of the pouch–jejunal iSelect genotyping array (Illumina Inc.). Thirteen SNPs were anastomosis standardized to about 12 mm. In the proximal not determinable because of technical reasons and were, RYGB procedure, the biliopancreatic limb was side to side thus, excluded from further analysis. The list of investigated anatomized to the jejunum 150-cm distal from the pouch–je- genetic variants is provided in Supplementary Table S1. All junal anastomosis (Roux-en Y limb length, 150 cm). In the dis- determined SNPs were in the Hardy–Weinberg equilibrium. tal RYGB procedure, the biliopancreatic limb was side to side anatomized to the ileum 60 to 100 cm proximal from Bauhin’s Statistics valve (common channel, 60–100 cm). The length to the bilio- To determine which of the BMI- or WHR-associated SNPs pancreatic limb was approximately 60 cm in the proximal and 60–100 cm in the distal RYGB procedure.[11] Patients who have a significant impact on the TFEQ factor outcome, the obtained the operation for a second time or underwent an genetic variants were included as covariates in a multiple lin- alternative intervention (e.g.,
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