ENPP1/PC-1 K121Q and other predictors of posttransplant diabetes.
Diabetes mellitus is a major cause of morbidity and mortality among transplanted patients. This study evaluated the role of the ENPP1 K121Q polymorphism and other variables known to affect diabetes risk in 115 nondiabetic and unrelated patients who underwent kidney transplant at our institution and had consented for use of genetic material (30% whites, 48% blacks, and 22% Hispanics). Thirty-six of these patients (30%) developed posttransplant diabetes mellitus (PTDM) within 1 year of observation from transplant. Black race, ENPP1 K121Q polymorphism, age, body mass index (BMI), and immunosuppressive medications were found to have the strongest associations with PTDM in the logistic regression and receiver operator characteristic (ROC) analysis. However, because ENPP1 K121Q is more common in Hispanics and in blacks, who also have higher PTDM prevalence, the studied genetic polymorphism did not exert independent predictive effect, whereas ethnicity, specifically black versus non-black, was the most robust predictor of PTDM. The model with the largest ROC area under the curve (AUC) of 0.80 was comprised of black/non-black, age, BMI, and tacrolimus treatment as significant predictors. A reduced model containing only ethnicity (black/non-black) and age as predictors yielded similar results (ROC AUC 0.78). We conclude that black race and age are major and not modifiable risk factors for PTDM. The specific role of ENPP1 K121Q on ethnic susceptibility to PTDM deserves further investigation in larger cohorts of transplanted patients.
The Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Magdalene
M
Szuszkiewicz
Jason
J
Bell
Miguel
M
Vazquez
Beverley
B
Adams-Huet
Scott M
SM
Grundy
Manisha
M
Chandalia
Nicola
N
Abate
D000328:Adult; D000367:Age Factors; D019943:Amino Acid Substitution; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000208:ethnology / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D011755:Pyrophosphatases / Q000235:genetics* / Q000502:physiology; D044469:Racial Groups / Q000235:genetics; D014180:Transplantation / Q000009:adverse effects* / Q000208:ethnology
D015415:Biomarkers; D018698:Glutamic Acid; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D008239:Lysine