Surgery for Obesity and Related Diseases ] (2014) 00–00 Original article Weight loss independent association of TCF7 L2 gene polymorphism with fasting blood glucose after Roux-en-Y gastric bypass in type 2 diabetic patients Konstantinos Rouskas, Ph.D a,b,c , Stephane Cauchi, Ph.D c,d,e , Violeta Raverdy, M.D. a,b,c , Loic Yengo, Ph.D c,d,e , Philippe Froguel, M.D., Ph.D. b,c,d,e , François Pattou, M.D., Ph.D a,b,c,d, * Q1 a INSERM, UMR 859 Biotherapies for Diabetes, Lille, France b CHRU, Lille, France c European Genetic Institute for Diabetes, Lille, France d University of Lille-Nord de France, Lille, France e CNRS UMR 8199, Institut Pasteur de Lille, France Received October 3, 2013; accepted December 30, 2013 Abstract Background: Roux-en-Y gastric bypass (RYGB) surgery improves glucose control in most but not all patients with type 2 diabetes mellitus (T2 DM). Transcription factor 7-like 2 (TCF7 L2) gene variation (rs7903146, C: wild-type allele, T: risk-allele) is the strongest contributor to T2 DM risk. Until now, there are no studies investigating gene interactions with changes of glycemia in obese patients with T2 DM after RYGB. The objective of this study was to assess the effect of TCF7 L2 genotype on RYGB-induced changes in glucose homeostasis in 99 obese patients with T2 DM at 1- year follow-up. Methods: Body mass index (BMI) and fasting blood glucose (FBG) were measured before and 1, 3, 6, and 12 months after RYGB. Genotyping was performed with TaqMan technology. The effect of the interaction between TCF7 L2 genotype and postoperative time on BMI and FBG changes was analyzed with a linear mixed model. Results: Preoperatively, there was no difference in BMI, FBG, and other diabetes associated traits between homozygous (CC) (n ¼ 49) and heterozygous (CT) or homozygous (TT) T risk-allele carriers (n ¼ 50). One year after RYGB, 48 out of 99 patients had glycosylated hemoglobin (HbA1 c) lower than 6.5% in absence of any antidiabetic medication. BMI decreased similarly in both groups (P ¼ .769, genotype-time interaction), however, the decrease in FBG over time was lower in T risk-allele carriers (P ¼ .016, genotype-time interaction). At 1 year, FBG was 6.42  2.98 mmol/ L in CT/TT versus 5.36  0.98 mmol/L in CC (P ¼ .022, t test). Conclusion: TCF7 L2 gene variation affected the decrease of FBG after RYGB in obese patients with T2 DM, independently of weight loss. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery. Keywords: Bariatric surgery; Type 2 Diabetes Mellitus; TCF7 L2 gene variation Roux-en-Y Gastric Bypass (RYGB) has emerged as an effective treatment for severe obesity as it results to a substantial and durable weight loss [1]. More interestingly, RYGB markedly ameliorates glucose homeostasis in most but not all patients with Type 2 Diabetes Mellitus (T2 DM) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 http://dx.doi.org/10.1016/j.soard.2013.12.016 1550-7289 r 2014 Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery. * Correspondence: Francois Pattou, General and Endocrine Surgery, Lille University Hospital, Lille, 59000 France. E-mail: fpattou@univ-lille2.fr