title: Effects of genetic variants in ADCY5, GIPR, GCKR and VPS13C on early impairment of glucose and insulin metabolism in children.
abstract: OBJECTIVE
  Recent genome-wide association studies identified novel candidate genes for fasting and 2 h blood glucose and insulin levels in adults. We investigated the role of four of these loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children.
  
  
  METHODS
  We genotyped four variants (rs2877716; rs1260326; rs10423928; rs17271305) in 638 Caucasian children with detailed metabolic testing including an oGTT and assessed associations with measures of glucose and insulin metabolism (including fasting blood glucose, insulin levels and insulin sensitivity/secretion indices) by linear regression analyses adjusted for age, sex, BMI-SDS and pubertal stage.
  
  
  RESULTS
  The major allele (C) of rs2877716 (ADCY5) was nominally associated with decreased fasting plasma insulin (P = 0.008), peak insulin (P = 0.009) and increased QUICKI (P = 0.016) and Matsuda insulin sensitivity index (P = 0.013). rs17271305 (VPS13C) was nominally associated with 2 h blood glucose (P = 0.009), but not with any of the insulin or insulin sensitivity parameters. We found no association of the GIPR and GCKR variants with parameters of glucose and insulin metabolism. None of the variants correlated with anthropometric traits such as height, WHR or BMI-SDS, which excluded potential underlying associations with obesity.
  
  
  CONCLUSIONS
  Our data on obese children indicate effects of genetic variation within ADCY5 in early impairment of insulin metabolism and VPS13C in early impairment of blood glucose homeostasis.
authors.affiliation: University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Windholz
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Kathrin
authors.initials: K
authors.lastname: Dittrich
authors.forename: Susann
authors.initials: S
authors.lastname: Blüher
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Antje
authors.initials: A
authors.lastname: Körner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000262:Adenylyl Cyclases / Q000235:genetics*; D000483:Alleles; D002648:Child; D003710:Demography; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human; D007328:Insulin; D011506:Proteins; D011964:Receptors, Gastrointestinal Hormone; C495324:VPS13C protein, human; C041086:gastric inhibitory polypeptide receptor; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V; D005947:Glucose