title: Association of TCF7L2 allelic variations with gastric function, satiation, and GLP-1 levels.
abstract: OBJECTIVE
  Genetic variation in transcription factor 7-like 2 (TCF7L2), a regulator of proglucagon processing, is reproducibly associated with type 2 diabetes. GLP-1 alters gastric function and increases satiation.
  
  
  OBJECTIVE
  Genetic variation in TCF7L2 is associated with satiation, gastric motor function, and GLP-1 concentrations.
  
  
  METHODS
  In 62 adults, a single nucleotide polymorphism (SNP) of TCF7L2 (rs7903146) was genotyped and associations with gastric emptying (GE) of solids and liquids, gastric volume (GV), and satiation (maximum tolerated volume and symptoms after nutrient drink test) were explored using a dominant genetic model, with gender and BMI as covariates. In 50 of the participants, we also measured plasma GLP-1 during fasting and after ingestion of a nutrient drink.
  
  
  RESULTS
  Presence of the T allele compared to CC genotype in rs7903146 SNP of the TCF7L2 gene was associated with reduced fasting GV (246.3 ± 11.4 mL for CC group, compared to 215.7 ± 11.4 mL for CT/TT group, p= 0.05) and accelerated GE t(1/2) of liquids (26.3 ± 2.0 minutes for CC compared to 17.7 ± 1.4 for CT/TT, p < 0.005). There was no significant association of rs7903146 SNP with GE of solids, gastric accommodation, satiation, fasting, or postprandial GLP-1.
  
  
  CONCLUSIONS
  Our data suggest TCF7L2 is associated with altered gastric functions that may predispose to obesity.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Vazquez-Roque
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Paula
authors.initials: P
authors.lastname: Carlson
authors.forename: Jeanette
authors.initials: J
authors.lastname: Laugen
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D052216:Glucagon-Like Peptide 1 / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D052336:Proglucagon / Q000378:metabolism; D011877:Radionuclide Imaging / Q000379:methods; D012527:Satiation / Q000502:physiology*; D013270:Stomach / Q000502:physiology*; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: D058118:Transcription Factor 7-Like 2 Protein; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1