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PTH-038 Genetic polymorphism of the CCK and CCK1 receptor genes does not affect gastric function or reported satiety
  1. R B Jones1,
  2. A Payton2,
  3. W E Ollier2,
  4. G J Dockray3,
  5. D G Thompson1
  1. 1Department of GI Sciences, University of Manchester, Salford, UK
  2. 2Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK
  3. 3Physiological Laboratory, University of Liverpool, Liverpool, UK

Abstract

Introduction The importance of genetic polymorphism in determining physiological responses is becoming increasingly apparent. Genetic polymorphism if the CCK1 receptor has been implicated in obesity1 and delayed gastric emptying.2 It is not known if common polymorphisms of CCK and the CCK1 receptor affect function and phenotype. Objectives: To determine if common genetic polymorphisms of the CCK or CCK1 receptor influence the magnitude of change in gastric emptying or feelings of fullness and hunger in response to CCK1 receptor antagonism.

Methods Saliva was obtained from 520 white Caucasoid individuals aged between 18 and 60 and analysed for single nucleotide polymorphisms (SNPs). Haplotype blocks were identified and 25 individuals (12 female, mean age 23, mean BMI 23.7) who were found to be homozygous for four different variants of these blocks (H1-4), underwent three liquid gastric emptying (GE) studies using the 13C acetate breath test, both with and without the CCK1 receptor antagonist dexloxiglumide (600 mg). These individuals filled in visual analogue scales (VAS) for hunger and fullness at 5-minute intervals for the duration of the studies (45 minutes). Mean per cent increase in gastric emptying with dexloxiglumide was calculated and compared across the genotypes.

Results No difference in the proportional increase in gastric emptying rate after dexloxiglumide was seen between the different haplotype groups: per cent increase in GE rate±SD: H1 (n=10) 35.8±20, H2 (n=5) 34.2±16, H3 (n=5) 34.3±28, H4 (n=5) 47.8±25. ANOVA p=0.66. No significant difference in changes in VAS scores for hunger or fullness was seen after dexloxiglumide between the different haplotype groups.

Conclusion Common genetic polymorphisms of the CCK or CCK1 receptor gene do not appear to affect the magnitude of CCK response to a nutrient stimulus. No difference in changes in reported feelings of fullness and hunger after dexloxiglumide are seen with genetic polymorphism of these genes.

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