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

Simonetta Bacci, Ornella Ludovico, Sabrina Prudente, Yuan Yuan Zhang, Rosa Di Paola, Davide Mangiacotti, Anna Rauseo, David S Nolan, Jill Duffy, Grazia Fini, Lucia Salvemini, Cesare Amico, Carlo Vigna, Fabio Pellegrini, Claudia Menzaghi, Alessandro Doria, Vincenzo Trischitta

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3021-3025
Number of pages5
JournalDiabetes
Volume54
Issue number10
DOIs
StatePublished - Oct 2005
Externally publishedYes

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Type 2 Diabetes Mellitus
Insulin Resistance
Coronary Artery Disease
Myocardial Infarction
Phenotype
Genes
Smoke
Italy
Odds Ratio

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Bacci, Simonetta; Ludovico, Ornella; Prudente, Sabrina; Zhang, Yuan Yuan; Di Paola, Rosa; Mangiacotti, Davide; Rauseo, Anna; Nolan, David S; Duffy, Jill; Fini, Grazia; Salvemini, Lucia; Amico, Cesare; Vigna, Carlo; Pellegrini, Fabio; Menzaghi, Claudia; Doria, Alessandro; Trischitta, Vincenzo.

In: Diabetes, Vol. 54, No. 10, 10.2005, p. 3021-3025.

Research output: Contribution to journalArticle

Bacci, S, Ludovico, O, Prudente, S, Zhang, YY, Di Paola, R, Mangiacotti, D, Rauseo, A, Nolan, DS, Duffy, J, Fini, G, Salvemini, L, Amico, C, Vigna, C, Pellegrini, F, Menzaghi, C, Doria, A & Trischitta, V 2005, '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', Diabetes, vol. 54, no. 10, pp. 3021-3025. https://doi.org/10.2337/diabetes.54.10.3021
Bacci, Simonetta ; Ludovico, Ornella ; Prudente, Sabrina ; Zhang, Yuan Yuan ; Di Paola, Rosa ; Mangiacotti, Davide ; Rauseo, Anna ; Nolan, David S ; Duffy, Jill ; Fini, Grazia ; Salvemini, Lucia ; Amico, Cesare ; Vigna, Carlo ; Pellegrini, Fabio ; Menzaghi, Claudia ; Doria, Alessandro ; Trischitta, Vincenzo. / 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. In: Diabetes. 2005 ; Vol. 54, No. 10. pp. 3021-3025.
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abstract = "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.",
author = "Simonetta Bacci and Ornella Ludovico and Sabrina Prudente and Zhang, {Yuan Yuan} and {Di Paola}, Rosa and Davide Mangiacotti and Anna Rauseo and Nolan, {David S} and Jill Duffy and Grazia Fini and Lucia Salvemini and Cesare Amico and Carlo Vigna and Fabio Pellegrini and Claudia Menzaghi and Alessandro Doria and Vincenzo Trischitta",
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T1 - 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

AU - Bacci, Simonetta

AU - Ludovico, Ornella

AU - Prudente, Sabrina

AU - Zhang, Yuan Yuan

AU - Di Paola, Rosa

AU - Mangiacotti, Davide

AU - Rauseo, Anna

AU - Nolan, David S

AU - Duffy, Jill

AU - Fini, Grazia

AU - Salvemini, Lucia

AU - Amico, Cesare

AU - Vigna, Carlo

AU - Pellegrini, Fabio

AU - Menzaghi, Claudia

AU - Doria, Alessandro

AU - Trischitta, Vincenzo

PY - 2005/10

Y1 - 2005/10

N2 - 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.

AB - 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.

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