title: Weight loss independent association of TCF7 L2 gene polymorphism with fasting blood glucose after Roux-en-Y gastric bypass in type 2 diabetic patients.
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 = 49) and heterozygous (CT) or homozygous (TT) T risk-allele carriers (n = 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 = .769, genotype-time interaction), however, the decrease in FBG over time was lower in T risk-allele carriers (P = .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 = .022, t test).
  
  
  CONCLUSIONS
  TCF7 L2 gene variation affected the decrease of FBG after RYGB in obese patients with T2 DM, independently of weight loss.
authors.affiliation: INSERM, UMR 859 Biotherapies for Diabetes, Lille, France; CHRU, Lille, France; European Genetic Institute for Diabetes, Lille, France.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Rouskas
authors.affiliation: European Genetic Institute for Diabetes, Lille, France; University of Lille-Nord de France, Lille, France; CNRS UMR 8199, Institut Pasteur de Lille, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Cauchi
authors.affiliation: INSERM, UMR 859 Biotherapies for Diabetes, Lille, France; CHRU, Lille, France; European Genetic Institute for Diabetes, Lille, France.
authors.forename: Violeta
authors.initials: V
authors.lastname: Raverdy
authors.affiliation: European Genetic Institute for Diabetes, Lille, France; University of Lille-Nord de France, Lille, France; CNRS UMR 8199, Institut Pasteur de Lille, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Yengo
authors.affiliation: CHRU, Lille, France; European Genetic Institute for Diabetes, Lille, France; University of Lille-Nord de France, Lille, France; CNRS UMR 8199, Institut Pasteur de Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.affiliation: INSERM, UMR 859 Biotherapies for Diabetes, Lille, France; CHRU, Lille, France; European Genetic Institute for Diabetes, Lille, France; University of Lille-Nord de France, Lille, France. Electronic address: fpattou@univ-lille2.fr.
authors.forename: François
authors.initials: F
authors.lastname: Pattou
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015390:Gastric Bypass; D006801:Humans; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D011110:Polymorphism, Genetic / Q000235:genetics; D013997:Time Factors; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D015431:Weight Loss; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein
keywords: Bariatric surgery; TCF7 L2 gene variation; Type 2 Diabetes Mellitus