title: Role of the ENPP1 K121Q polymorphism in glucose homeostasis.
abstract: OBJECTIVE
  To study the role of the ENPP1 Q121 variant on glucose homeostasis in whites from Italy.
  
  
  METHODS
  We conducted case-control studies in 764 adults (from two independent samples of 289 nonobese and 485 obese individuals) and 240 overweight/obese children undergoing oral glucose tolerance testing (OGTT). Early-phase insulin secretion and insulin sensitivity (the insulinogenic index and the insulin sensitivity index) and their interplay (the disposition index) were calculated.
  
  
  RESULTS
  In adult subjects, glucose profiles during OGTT were significantly (P = 2 x 10(-2)) different across K121Q genotype groups and higher in QQ than KK individuals (P = 5 x 10(-2)). The insulinogenic index was significantly reduced in QQ (18.5 +/- 3.4) compared with both KK (31.6 +/- 1.0; P = 2.2 x 10(-7)) and KQ (30.5 +/- 1.5; P = 3.2 x 10(-6)) individuals. KQ individuals also showed a reduced insulin sensitivity index compared with KK subjects (P = 3.6 x 10(-2)). The disposition index was lower in QQ carriers than in KQ and KK individuals (P = 8 x 10(-3) and 4 x 10(-4), respectively) and lower in KQ than in KK individuals (P = 3 x 10(-2)). Data obtained in overweight/obese children were very similar to those observed in adults, with QQ individuals showing (compared with KQ and KK subjects) a reduced insulinogenic index (P = 7 x 10(-3) and 2 x 10(-2), respectively) and disposition index (P = 2 x 10(-2) and 7 x 10(-3), respectively).
  
  
  CONCLUSIONS
  Homozygous carriers of the ENPP1 Q121 variant are characterized by an altered glucose homeostasis. Reduced early-phase insulin secretion and inefficient interplay between insulin secretion and sensitivity, which occur at early ages, are major determinants of this defect.
authors.affiliation: Unit of Endocrinology, Department of Internal and Specialistic Medicine, University of Catania Medical School, Garibaldi Hospital, Catania, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Baratta
authors.forename: Paola
authors.initials: P
authors.lastname: Rossetti
authors.forename: Sabrina
authors.initials: S
authors.lastname: Prudente
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Barbetti
authors.forename: Dora
authors.initials: D
authors.lastname: Sudano
authors.forename: Angela
authors.initials: A
authors.lastname: Nigro
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Farina
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
authors.forename: Lucia
authors.initials: L
authors.lastname: Frittitta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002648:Child; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D014644:Genetic Variation; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007558:Italy; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011755:Pyrophosphatases / Q000235:genetics*; D012016:Reference Values; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D007328:Insulin; D004247:DNA; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D005947:Glucose
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