title: Association of UCP-3 rs1626521 with obesity and stomach functions in humans.
abstract: OBJECTIVE
  To examine the association of gene variants of uncoupling proteins (UCP)-2 and -3 with obesity and gastrointestinal (GI) traits.
  
  
  METHODS
  In 255 overweight or obese adults, the associations of gene variants in UCP-2 (-3474, rs659366) and UCP-3 (rs1626521, rs2075577, rs15763) with body weight (BW) and GI traits were studied. Gene variants were genotyped by TaqMan® assay. The associations of genotypes with BW and GI traits (gastric emptying, gastric volume, satiety by buffet meal, satiation by nutrient drink test and GI hormones) were assessed using ANOVA corrected for false detection rate (FDR).
  
  
  RESULTS
  A novel UCP-3 gene variant, rs1626521, was identified; it was associated with BW (P = 0.039), waist circumference (P = 0.035), and significantly higher postprandial gastric volume (P = 0.003) and calories ingested at buffet meal (P = 0.006, both significant with FDR). In a subgroup of 11 participants, rs1626521 was also associated with reduced mitochondrial bioenergetics efficiency in skeletal muscle (P = 0.051). In an in vitro study in HEK293 cells, rs1626521 reduced UCP-3 protein expression (P = 0.049). Associations detected between other genotypes and GI traits were nonsignificant with FDR.
  
  
  CONCLUSIONS
  A newly identified functional variant (rs1626521) in UCP-3 affects postprandial gastric functions and satiety and may contribute to weight gain and alter human mitochondrial function.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Acosta
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Andrea
authors.initials: A
authors.lastname: Shin
authors.forename: Maria I
authors.initials: MI
authors.lastname: Vazquez-Roque
authors.forename: Johanna
authors.initials: J
authors.lastname: Iturrino
authors.forename: Ian R
authors.initials: IR
authors.lastname: Lanza
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
authors.forename: Duane
authors.initials: D
authors.lastname: Burton
authors.forename: Jessica
authors.initials: J
authors.lastname: O'Neill
authors.forename: Deborah
authors.initials: D
authors.lastname: Eckert
authors.forename: Paula
authors.initials: P
authors.lastname: Carlson
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000328:Adult; D005746:Gastric Emptying / Q000235:genetics* / Q000502:physiology; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period / Q000502:physiology; D012527:Satiation / Q000502:physiology; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3