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

17 Citations (Scopus)

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

Fingerprint

Kidney Diseases
Diabetic Nephropathies
Disease Progression
Genes
Genotype
Diabetic Retinopathy
Glomerular Filtration Rate
Proteinuria
Longitudinal Studies
Insulin Resistance
Creatinine
Heart Failure
Cross-Sectional Studies
Kidney
Serum

Keywords

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

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

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

In: Nephrology Dialysis Transplantation, Vol. 17, No. 8, 2002, p. 1402-1407.

Research output: Contribution to journalArticle

De Cosmo, S, Miscio, G, Zucaro, L, Margaglione, M, Argiolas, A, Thomas, S, Piras, G, Trevisan, R, Perin, PC, 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, vol. 17, no. 8, pp. 1402-1407.
De Cosmo, Salvatore ; Miscio, Giuseppe ; Zucaro, Luigi ; Margaglione, Maurizio ; Argiolas, Alessandra ; Thomas, Stephen ; Piras, Giampiero ; Trevisan, Roberto ; Perin, Paolo Cavallo ; Bacci, Simonetta ; Frittitta, Lucia ; Pizzuti, Antonio ; Tassi, Vittorio ; Di Minno, Giovanni ; Viberti, Giancarlo ; Trischitta, Vincenzo. / 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. In: Nephrology Dialysis Transplantation. 2002 ; Vol. 17, No. 8. pp. 1402-1407.
@article{7391c352798f4380980bf7d83668e76e,
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. 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.",
keywords = "Albuminuria, End-stage renal failure, Gene polymorphism, Gene-gene interaction, Type 1 diabetes",
author = "{De Cosmo}, Salvatore and Giuseppe Miscio and Luigi Zucaro and Maurizio Margaglione and Alessandra Argiolas and Stephen Thomas and Giampiero Piras and Roberto Trevisan and Perin, {Paolo Cavallo} and Simonetta Bacci and Lucia Frittitta and Antonio Pizzuti and Vittorio Tassi and {Di Minno}, Giovanni and Giancarlo Viberti and Vincenzo Trischitta",
year = "2002",
language = "English",
volume = "17",
pages = "1402--1407",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - The role of PC-1 and ACE genes in diabetic nephropathy in type 1 diabetic patients

T2 - Evidence for a polygenic control of kidney disease progression

AU - De Cosmo, Salvatore

AU - Miscio, Giuseppe

AU - Zucaro, Luigi

AU - Margaglione, Maurizio

AU - Argiolas, Alessandra

AU - Thomas, Stephen

AU - Piras, Giampiero

AU - Trevisan, Roberto

AU - Perin, Paolo Cavallo

AU - Bacci, Simonetta

AU - Frittitta, Lucia

AU - Pizzuti, Antonio

AU - Tassi, Vittorio

AU - Di Minno, Giovanni

AU - Viberti, Giancarlo

AU - Trischitta, Vincenzo

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Albuminuria

KW - End-stage renal failure

KW - Gene polymorphism

KW - Gene-gene interaction

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=0035993273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035993273&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 1402

EP - 1407

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 8

ER -