PMID- 10480624
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 48
IP  - 9
DP  - 1999 Sep
TI  - A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is
      strongly associated with insulin resistance.
PG  - 1881-4
AB  - The genes responsible for insulin resistance are poorly defined. Plasma cell
      differentiation antigen (PC-1) glycoprotein inhibits insulin receptor signaling
      and is associated with insulin resistance. We describe here a novel polymorphism 
      in exon 4 of the PC-1 gene (K121Q) and demonstrate that it is strongly associated
      with insulin resistance in 121 healthy nonobese (BMI <30 kg/m2) nondiabetic (by
      oral glucose tolerance test [OGTT]) Caucasians from Sicily. Compared with 80 KK
      subjects, Q allele carriers (n = 41, 39 KQ and 2 QQ) showed higher glucose and
      insulin levels during OGTT (P < 0.001 by two-way analysis of variance) and
      insulin resistance by euglycemic clamp (M value = 5.25 +/- 1.38 [n = 24] vs. 6.30
      +/- 1.39 mg x kg(-1) x min(-1) [n = 49], P = 0.005). Q carriers had higher risk
      of being hyperinsulinemic and insulin resistant (odds ratio [CI]: 2.99
      [1.28-7.0], P < 0.001). Insulin receptor autophosphorylation was reduced (P <
      0.01) in cultured skin fibroblasts from KQ versus KK subjects. Skeletal muscle
      PC-1 content was not different in 11 KQ versus 32 KK subjects (33 +/- 16.1 vs.
      17.5 +/- 15 ng/mg protein, P = 0.3). These results suggest a cause-effect
      relationship between the Q carrying genotype and the insulin resistance
      phenotype, and raise the possibility that PC-1 genotyping could identify
      individuals who are at risk of developing insulin resistance, a condition that
      predisposes to type 2 diabetes and coronary artery disease.
FAU - Pizzuti, A
AU  - Pizzuti A
AD  - Divisione e Unita di Ricerca di Endocrinologia, Istituto Scientifico Ospedale
      Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
FAU - Frittitta, L
AU  - Frittitta L
FAU - Argiolas, A
AU  - Argiolas A
FAU - Baratta, R
AU  - Baratta R
FAU - Goldfine, I D
AU  - Goldfine ID
FAU - Bozzali, M
AU  - Bozzali M
FAU - Ercolino, T
AU  - Ercolino T
FAU - Scarlato, G
AU  - Scarlato G
FAU - Iacoviello, L
AU  - Iacoviello L
FAU - Vigneri, R
AU  - Vigneri R
FAU - Tassi, V
AU  - Tassi V
FAU - Trischitta, V
AU  - Trischitta V
LA  - eng
PT  - Clinical Trial
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Membrane Glycoproteins)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.1 (ectonucleotide pyrophosphatase phosphodiesterase 1)
RN  - EC 3.6.1.- (Pyrophosphatases)
SB  - IM
MH  - Adult
MH  - Analysis of Variance
MH  - Cells, Cultured
MH  - Exons
MH  - Female
MH  - Genetic Code
MH  - Glucose Clamp Technique
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Insulin Resistance/*genetics
MH  - Male
MH  - Membrane Glycoproteins/*genetics
MH  - *Phosphoric Diester Hydrolases
MH  - Phosphorylation
MH  - *Polymorphism, Genetic
MH  - *Pyrophosphatases
MH  - Reference Values
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.2337/diabetes.48.9.1881 [doi]
PST - ppublish
SO  - Diabetes. 1999 Sep;48(9):1881-4. doi: 10.2337/diabetes.48.9.1881.