title: The role of PC-1 and ACE genes in diabetic nephropathy in type 1 diabetic patients: evidence for a polygenic control of kidney disease progression.
abstract: BACKGROUND
  The DD genotype of the ACE gene predisposes to faster diabetic nephropathy (DN) progression but its role in DN development is more controversial. We reported previously, in type 1 diabetic patients, an association between faster DN progression and the PC-1 gene Q121 variant, which associates with insulin resistance in non-diabetic subjects. We investigated here whether the combination of the ACE DD genotype and the PC-1 Q121 variant predicts the development and/or progression of DN in type 1 diabetic patients.
  
  
  METHODS
  Type 1 diabetic patients either with (n=159) or without (n=122) nephropathy were evaluated in a cross-sectional study. DN was defined as the presence of microalbuminuria or persistent proteinuria in a subject with more than 10-year duration of disease and concomitant diabetic retinopathy, and with no evidence of heart failure or other renal disease. Seventy-five (47 male/28 female) type 1 diabetic patients with nephropathy in whom retrospective information with repeated measurements of serum creatinine was available, were analysed in a longitudinal study.
  
  
  RESULTS
  No association of the PC-1 Q121 variant and the ACE D/D genotype with DN development was observed. However, the ACE DD genotype and the PC-1 Q121 variant were associated, both independently (P=0.02 and P=0.025, respectively) or in combination (P=0.02), with a faster rate of glomerular filtration rate decline. An interaction (P=0.03) was observed between the two genes in increasing the individual patient's risk of being a fast progressor.
  
  
  CONCLUSIONS
  Our data suggest that, in type 1 diabetic patients, the ACE and the PC-1 genes interact in increasing the individual risk of having a faster DN progression.
authors.affiliation: Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza San Giovanni Rotondo (FG), Italy. endocrinologia@operapadrepio.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Miscio
authors.forename: Luigi
authors.initials: L
authors.lastname: Zucaro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Margaglione
authors.forename: Alessandra
authors.initials: A
authors.lastname: Argiolas
authors.forename: Stephen
authors.initials: S
authors.lastname: Thomas
authors.forename: Giampiero
authors.initials: G
authors.lastname: Piras
authors.forename: Roberto
authors.initials: R
authors.lastname: Trevisan
authors.forename: Paolo Cavallo
authors.initials: PC
authors.lastname: Perin
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bacci
authors.forename: Lucia
authors.initials: L
authors.lastname: Frittitta
authors.forename: Antonio
authors.initials: A
authors.lastname: Pizzuti
authors.forename: Vittorio
authors.initials: V
authors.lastname: Tassi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Minno
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Viberti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
mesh_terms: D000328:Adult; D017668:Age of Onset; D000419:Albuminuria; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D002784:Cholesterol; D003404:Creatinine; D006442:Glycated Hemoglobin; D007703:Peptidyl-Dipeptidase A; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D014280:Triglycerides; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1