TY - JOUR
T1 - Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus
AU - Van Ittersum, Frans J.
AU - De Man, Angelique M.E.
AU - Thijssen, Sandra
AU - De Knijff, Peter
AU - Slagboom, Eline
AU - Smulders, Yvo
AU - Tarnow, Lise
AU - Donker, Ab J.M.
AU - Bilo, Henk J.G.
AU - Stehouwer, Coen D.A.
PY - 2000/1/1
Y1 - 2000/1/1
N2 - Objective. Patients with insulin-dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascular diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among populations. Methods. In 257 Dutch IDDM patients (188 with urinary albumin excretion (UAE) < 30 mg/24 h), logistic regression analysis was used to study the relationships among, on the one hand, the insertion/deletion gene polymorphism of the angiotensin-converting enzyme gene (ACE-ID), the M235T gene polymorphism of the angiotensinogen gene (AGT-M235T), and the A1166C gene polymorphism of the angiotensin type 1 receptor gene (AT1-A1166C), and, on the other hand, UAE, retinopathy, hypertension, and coronary heart disease. Results. The T-allele of the AGT-M235T polymorphism was associated with an increased risk of an elevated UAE (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.06-8.61), but only when interaction with the D-allele of the ACE-ID polymorphism was considered. A previously described positive interaction between the T-allele of the AGT-M235T polymorphism and the D-allele of the ACE-ID polymorphism could not be confirmed. The T-allele was also associated with an increased risk of retinopathy (OR 3.89, 95% CI 1.79-8.47). The CC-genotype of the AT1-A1166C polymorphism was associated with hypertension (OR 3.58; 95% CI 1.23-10.37). Conclusions. In a Dutch IDDM population, including 69 patients with (incipient) diabetic nephropathy, the T-allele of the AGT-M235T polymorphism is associated with an elevated UAE and diabetic retinopathy and the CC-genotype of the AT1-A1166C polymorphism is associated with hypertension. A previously described interaction between the AGT-M235T and the ACE-ID polymorphisms could not be confirmed. Since the number of nephropathic patients in this study is small, these conclusions must be interpreted with caution.
AB - Objective. Patients with insulin-dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascular diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among populations. Methods. In 257 Dutch IDDM patients (188 with urinary albumin excretion (UAE) < 30 mg/24 h), logistic regression analysis was used to study the relationships among, on the one hand, the insertion/deletion gene polymorphism of the angiotensin-converting enzyme gene (ACE-ID), the M235T gene polymorphism of the angiotensinogen gene (AGT-M235T), and the A1166C gene polymorphism of the angiotensin type 1 receptor gene (AT1-A1166C), and, on the other hand, UAE, retinopathy, hypertension, and coronary heart disease. Results. The T-allele of the AGT-M235T polymorphism was associated with an increased risk of an elevated UAE (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.06-8.61), but only when interaction with the D-allele of the ACE-ID polymorphism was considered. A previously described positive interaction between the T-allele of the AGT-M235T polymorphism and the D-allele of the ACE-ID polymorphism could not be confirmed. The T-allele was also associated with an increased risk of retinopathy (OR 3.89, 95% CI 1.79-8.47). The CC-genotype of the AT1-A1166C polymorphism was associated with hypertension (OR 3.58; 95% CI 1.23-10.37). Conclusions. In a Dutch IDDM population, including 69 patients with (incipient) diabetic nephropathy, the T-allele of the AGT-M235T polymorphism is associated with an elevated UAE and diabetic retinopathy and the CC-genotype of the AT1-A1166C polymorphism is associated with hypertension. A previously described interaction between the AGT-M235T and the ACE-ID polymorphisms could not be confirmed. Since the number of nephropathic patients in this study is small, these conclusions must be interpreted with caution.
KW - Angiotensin II type 1 receptor gene polymorphism
KW - Angiotensin-converting enzyme gene polymorphism
KW - Angiotensinogen gene polymorphism
KW - Complications
KW - Insulin-dependent diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=0034123846&partnerID=8YFLogxK
U2 - 10.1093/ndt/15.7.1000
DO - 10.1093/ndt/15.7.1000
M3 - Article
C2 - 10862638
AN - SCOPUS:0034123846
SN - 0931-0509
VL - 15
SP - 1000
EP - 1007
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 7
ER -