title: Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus.
abstract: 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.
authors.affiliation: Department of Medicine, Institute for Cardiovascular Research, Vrije Universiteit Amsterdam, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: van Ittersum
authors.forename: A M
authors.initials: AM
authors.lastname: de Man
authors.forename: S
authors.initials: S
authors.lastname: Thijssen
authors.forename: P
authors.initials: P
authors.lastname: de Knijff
authors.forename: E
authors.initials: E
authors.lastname: Slagboom
authors.forename: Y
authors.initials: Y
authors.lastname: Smulders
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.forename: A J
authors.initials: AJ
authors.lastname: Donker
authors.forename: H J
authors.initials: HJ
authors.lastname: Bilo
authors.forename: C D
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000235:genetics; D000808:Angiotensinogen / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics; D004251:DNA Transposable Elements; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A