title: A preliminary candidate genotype-intermediate phenotype study of satiation and gastric motor function in obesity.
abstract: Stomach motility contributes significantly to fullness sensation while eating and cessation of food intake in humans. Genes controlling adrenergic and serotonergic mechanisms (ADRA2A, GNB3, and SLC6A4) affect gastric emptying (GE), volume (GV), and satiation. Fat mass and obesity-associated gene (FTO) is linked with satiety. Our aim was to examine the association of these candidate genes with stomach functions that signal postprandial fullness: GE, GV, and maximum tolerated volume (MTV). These biomarkers constitute a component of the intermediate phenotype of satiation. A total of 62 overweight or obese participants underwent genotyping of the candidate genes, and validated measurements of GE of solids and liquids by scintigraphy, fasting and postprandial change in GV by SPECT (single photon emission computed tomography), and MTV by nutrient drink test. These markers of satiation were compared for 38 genetic variants in ADRA2A, ADR2C, ADRB3, uncoupling protein (UCP)-2 and -3, GNB3, FTO, and SLC6A4 using a recessive model of inheritance. ADRA2A, ADR2C, UCP-3, GNB3, and FTO loci were significantly associated with the intermediate phenotype markers of satiation: ADR2C (Ins-Del322_325) with accelerated GE; GNB3 (rs1047776) with delayed GE; ADRA2A (rs491589 and rs553668) and GNB3 (rs2269355, rs10849527, and rs3759348) with decreased postprandial GV; ADRA2A (rs3750625) and GNB3 (rs4963517 and rs1129649) with increased postprandial GV; UCP-3 (rs1685356) with increased MTV, and FTO (rs9939609) decreased MTV. Genetic susceptibility to postprandial satiation can be identified through intermediate phenotype markers. With independent validation, these markers may guide patient selection of weight-loss therapies directed at gastric motor functions.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papathanasopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Carlson
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Sara J Linker
authors.initials: SJ
authors.lastname: Nord
authors.forename: Duane D
authors.initials: DD
authors.lastname: Burton
authors.forename: Suwebatu T
authors.initials: ST
authors.lastname: Odunsi
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001069:Appetite Regulation / Q000235:genetics / Q000502:physiology; D005260:Female; D005753:Gastric Mucosa / Q000502:physiology; D005769:Gastrointestinal Motility / Q000235:genetics* / Q000502:physiology*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011877:Radionuclide Imaging; D012527:Satiation / Q000502:physiology*; D055815:Young Adult