The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction.
Insulin resistance (IR) is pathogenic for type 2 diabetes and coronary artery disease (CAD). The K121Q polymorphism of the ENPP1/PC-1 gene is associated with IR. Our aim was to investigate the role of the 121Q variant on the risk of type 2 diabetes and CAD. Nondiabetic control subjects (n = 638), type 2 diabetic patients without CAD (n = 535), and type 2 diabetic patients with CAD (n = 434) from Italy and the U.S. were studied. The proportion of 121Q carriers progressively increased in the three groups (27.4, 28.8, and 33.2%, respectively; adjusted P value = 0.027). Among diabetic patients (n = 969), 121Q carriers had an increased risk of developing type 2 diabetes before the age of 65 years (adjusted odds ratio [OR] 2.26, 95% CI 1.26-4.03; P = 0.006) and having a myocardial infarction (MI) (n = 156) by 50 years of age (3.17, 1.46-6.88, P = 0.007). The 121Q variant was also associated with an increased risk for CAD (1.47, 1.01-2.18; P = 0.049) in diabetic patients who did not smoke (n = 546). In conclusion, the ENPP1/PC-1 121Q variant is associated with a progressive deterioration of the IR-atherogenic phenotype; among diabetic individuals, it is also associated with earlier onset of type 2 diabetes and MI.
Bacci
Simonetta
S
Unit of Endocrinology, CSS Scientific Institute, San Giovanni Rotondo, Italy. dnnwba@tin.it
Ludovico
Ornella
O
Prudente
Sabrina
S
Zhang
Yuan-Yuan
YY
Di Paola
Rosa
R
Mangiacotti
Davide
D
Rauseo
Anna
A
Nolan
David
D
Duffy
Jill
J
Fini
Grazia
G
Salvemini
Lucia
L
Amico
Cesare
C
Vigna
Carlo
C
Pellegrini
Fabio
F
Menzaghi
Claudia
C
Doria
Alessandro
A
Trischitta
Vincenzo
V
D000328:Adult; D000368:Aged; D000375:Aging; D050197:Atherosclerosis / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic; D011755:Pyrophosphatases / Q000235:genetics*
D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases