title: Endothelial nitric oxide synthase gene intron 4 polymorphism predicts new onset diabetes mellitus after transplantation in kidney allograft recipients treated with cyclosporin A.
abstract: BACKGROUND
  Nitric oxide (NO), synthesized from LS: -arginine by the enzyme endothelial nitric oxide synthase (eNOS), is a potent vasodilator and has been implicated in mediating insulin-induced uptake and metabolism of glucose in skeletal muscle. Polymorphisms of the eNOS gene have been associated with altered eNOS activity and NO levels. Although several factors have been demonstrated for new onset diabetes mellitus after transplantation (NODAT), determining a genetic susceptibility for all patients requires further study. In our study, we evaluated the relationship between eNOS gene intron 4 polymorphism and NODAT in kidney allograft recipients.
  
  
  METHODS
  A total of 82 consecutive patients who received their first kidney transplantation and maintained graft function for at least a 12-month post-transplant period and who used triple therapy including cyclosporin A (CsA) for maintenance immunosuppression were included. PCR-RFLP was used for genetic analyses.
  
  
  RESULTS
  Nine of 82 patients (11%) developed NODAT. Concerning the prevalence of eNOS intron 4 gene polymorphism, a significantly higher percentage of 4a allele carriers developed NODAT than non-carriers [6/26 (23.1%) versus 3/56 (5.4%), P = 0.02]. Compared with non-diabetics, NODAT patients were older (P = 0.04), had higher rate of hepatitis C (P < 0.05) and higher body mass index at the time of transplantation (P = 0.03). In regression analyses, having a 4a allele of the eNOS gene intron 4 polymorphism (P = 0.02) and HCV seropositivity (P = 0.03) were found to be independent risk factors for the development of NODAT.
  
  
  CONCLUSIONS
  These findings suggest that carrying a 4a allele of the eNOS gene intron 4 polymorphism is associated with NODAT. This may help us to further understand the individual risk for development of NODAT in kidney allograft recipients under CsA treatment.
authors.affiliation: Department of Nephrology, Ankara University School of Medicine, Ankara, Turkey. ihsanerg@yahoo.com
authors.forename: Ihsan
authors.initials: I
authors.lastname: Ergün
authors.forename: Kenan
authors.initials: K
authors.lastname: Keven
authors.forename: Sule
authors.initials: S
authors.lastname: Sengül
authors.forename: Halil Gürhan
authors.initials: HG
authors.lastname: Karabulut
authors.forename: Ilhan
authors.initials: I
authors.lastname: Kurultak
authors.forename: Zeki
authors.initials: Z
authors.lastname: Soypacaci
authors.forename: Bülent
authors.initials: B
authors.lastname: Erbay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007438:Introns / Q000235:genetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000235:genetics*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D052250:Nitric Oxide Synthase Type III