TY - JOUR
T1 - 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
AU - De Cosmo, S
AU - Miscio, G
AU - Zucaro, L
AU - Margaglione, M
AU - Argiolas, A
AU - Thomas, S
AU - Piras, G
AU - Trevisan, R
AU - Perin, P C
AU - Bacci, S
AU - Frittitta, L
AU - Pizzuti, A
AU - Tassi, V
AU - Di Minno, G
AU - Viberti, G
AU - Trischitta, V
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-I 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-I 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.
UR - http://www.scopus.com/inward/record.url?scp=0035993273&partnerID=8YFLogxK
U2 - 10.1093/ndt/17.8.1402
DO - 10.1093/ndt/17.8.1402
M3 - Article
SN - 1460-2385
VL - 17
SP - 1402
EP - 1407
JO - Nephrology, Dialysis, Transplantation
JF - Nephrology, Dialysis, Transplantation
IS - 8
ER -
