Association of tcf7l2 allelic variations with gastric function, satiation, and glp-1 levels

Maria I Vazquez Roque, Michael Camilleri, Adrian Vella, Paula Carlson, Jeanette Laugen, Alan R. Zinsmeister

Research output: Contribution to journalArticle

10 Citations (Scopus)

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. Hypothesis: 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 t1/2 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. Conclusion: Our data suggest TCF7L2 is associated with altered gastric functions that may predispose to obesity.

Original languageEnglish (US)
Pages (from-to)183-187
Number of pages5
JournalClinical and Translational Science
Volume4
Issue number3
DOIs
StatePublished - Jun 2011

Fingerprint

T Cell Transcription Factor 1
Satiation
Glucagon-Like Peptide 1
Stomach
Polymorphism
Gastric Emptying
Nucleotides
Single Nucleotide Polymorphism
Fasting
Nutrients
Proglucagon
Liquids
Food
Medical problems
Genetic Models
Type 2 Diabetes Mellitus
Genes
Plasmas
Obesity
Eating

Keywords

  • Gastric emptying
  • Gastric volume
  • Obesity
  • Prediabetes
  • TCF7L2

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Association of tcf7l2 allelic variations with gastric function, satiation, and glp-1 levels. / Vazquez Roque, Maria I; Camilleri, Michael; Vella, Adrian; Carlson, Paula; Laugen, Jeanette; Zinsmeister, Alan R.

In: Clinical and Translational Science, Vol. 4, No. 3, 06.2011, p. 183-187.

Research output: Contribution to journalArticle

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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. Hypothesis: 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 t1/2 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. Conclusion: Our data suggest TCF7L2 is associated with altered gastric functions that may predispose to obesity.",
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N2 - 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. Hypothesis: 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 t1/2 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. Conclusion: Our data suggest TCF7L2 is associated with altered gastric functions that may predispose to obesity.

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