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

Salvatore De Cosmo, Giuseppe Miscio, Luigi Zucaro, Maurizio Margaglione, Alessandra Argiolas, Stephen Thomas, Giampiero Piras, Roberto Trevisan, Paolo Cavallo Perin, Simonetta Bacci, Lucia Frittitta, Antonio Pizzuti, Vittorio Tassi, Giovanni Di Minno, Giancarlo Viberti, Vincenzo Trischitta

Research output: Contribution to journalArticle

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. Conclusion. 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.

Original languageEnglish
Pages (from-to)1402-1407
Number of pages6
JournalNephrology Dialysis Transplantation
Volume17
Issue number8
Publication statusPublished - 2002

Keywords

  • Albuminuria
  • End-stage renal failure
  • Gene polymorphism
  • Gene-gene interaction
  • Type 1 diabetes

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    De Cosmo, S., Miscio, G., Zucaro, L., Margaglione, M., Argiolas, A., Thomas, S., Piras, G., Trevisan, R., Perin, P. C., Bacci, S., Frittitta, L., Pizzuti, A., Tassi, V., Di Minno, G., Viberti, G., & Trischitta, V. (2002). 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. Nephrology Dialysis Transplantation, 17(8), 1402-1407.