title: Genetic and clinical risk factors of new-onset diabetes after transplantation in Hispanic kidney transplant recipients.
abstract: BACKGROUND
  New-onset diabetes after transplantation (NODAT) is one of the major complications after transplantation and is associated with reduced overall patient and graft survival. The objective of this study was to determine the genetic and clinical risk factors for NODAT in Hispanic kidney transplant recipients.
  
  
  METHODS
  Hispanic kidney allograft recipients without evidence of preexisting diabetes who developed NODAT (n=133) were studied using Hispanic kidney transplant recipients with no evidence of diabetes as a control group (n=170). NODAT was defined as fasting glucose levels ≥126 mg/dL on two or more occasions or patients taking any insulin or oral hypoglycemic agents 1 month or later after kidney transplantation. Fourteen alleles in nine genes were genotyped and other patients' clinical data with genotype data were analyzed by logistic regression.
  
  
  RESULTS
  Among 14 alleles, hepatocyte nuclear factor 4 alpha (HNF4A) AA (rs2144908, odds ratio [OR]=1.96, confidence interval [CI]=1.08-3.50, P=0.010), HNF4A TT (rs1884614, OR=2.44, CI=1.42-4.48, P=0.002), and insulin receptor substrate 1 AA+AG (rs1801278, OR=2.71, CI=1.16-6.89, P=0.021) remained significant after logistic regression. Among the clinical factors, average age (OR=1.01, CI=1.00-1.08, P=0.048), sirolimus (OR=5.36, CI=3.02-10.4, P=0.001), deceased donor (OR=1.96, CI=1.16-2.94, P=0.015), and acute rejection (OR=2.92, CI=1.31-5.77, P=0.009) remained significant after logistic regression.
  
  
  CONCLUSIONS
  This study indicates that polymorphism of two alleles of HNF-4A gene (rs2144908 and rs1884614) and insulin receptor substrate 1 (rs1801278) are significantly associated with NODAT in kidney transplant patients with Hispanic ethnicity. In the case of clinical factors, older age (>50 year), deceased donor type, acute rejection, and sirolimus use are associated with NODAT in Hispanic kidney transplant recipients.
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy, University of Kansas, Kansas City, KS, USA. jyang2@kumc.edu
authors.forename: Jaewook
authors.initials: J
authors.lastname: Yang
authors.forename: Ian I
authors.initials: II
authors.lastname: Hutchinson
authors.forename: Tariq
authors.initials: T
authors.lastname: Shah
authors.forename: David I
authors.initials: DI
authors.lastname: Min
mesh_terms: D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003920:Diabetes Mellitus / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000208:ethnology / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D016030:Kidney Transplantation / Q000208:ethnology*; D016015:Logistic Models; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; C526292:IRS1 protein, human; D007166:Immunosuppressive Agents; D055504:Insulin Receptor Substrate Proteins; D020123:Sirolimus