title: Angiotensinogen gene T235 variant: a marker for the development of persistent microalbuminuria in children and adolescents with type 1 diabetes mellitus.
abstract: OBJECTIVE
  We examined genetic polymorphisms in the renin-angiotensin system (RAS) coding for angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) for angiotensinogen (AGT) M235T and angiotensin II receptor type 1 (AGTR1) A1166C as predictors for the development of microalbuminuria (MA) in children with type 1 diabetes mellitus (T1DM).
  
  
  METHODS
  Four hundred fifty-three (215 males, 238 females) T1DM children [median (interquartile range): age, 16.7 years (13.9-18.3); diabetes duration, 6.9 years (3.3-10.8); age at diagnosis, 9.1 years (5.8-11.8)] were followed prospectively from diagnosis until the development of MA (two of three consecutive overnight urine samples with albumin excretion rates of > or =20 and <200 microg/min). Kaplan-Meier survival curves and Cox proportional multivariate model estimated the probability of developing MA and the relative risk for MA among different variables.
  
  
  RESULTS
  MA developed in 41 (9.1%) subjects. The frequencies of genotypes were as follows: ACE-II 112 (25%), ACE-ID 221 (49%), and ACE-DD 117 (26%) (n=450); AGT-MM 144 (32%), AGT-MT 231 (51%), and AGT-TT 77 (17%) (n=452); AGTR1-AA 211 (47%), AGTR1-AC 204 (45%), and AGTR1-CC 37 (8%) (n=452). The cumulative risk for the development of MA was higher in ACE-DD versus ACE-ID/II groups (log-rank test, P=.05), and a trend was noticed when AGT-TT was compared to AGT-MT/MM groups (log-rank test, P=.08). AGT-TT polymorphism conferred a fourfold increased risk for MA compared to AGT-MM/MT (hazard ratio=3.8; 95% confidence interval=1.43-10.3; P=.008).
  
  
  CONCLUSIONS
  Our findings suggest that RAS gene polymorphism at AGT M235T is a strong predictor for early MA in young T1DM subjects.
authors.affiliation: Department of Pediatric Endocrinology and Diabetes, Princess Margaret Hospital, Perth, WA, Australia. patricG4@chw.edu.au
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Gallego
authors.forename: Neil
authors.initials: N
authors.lastname: Shephard
authors.forename: Max K
authors.initials: MK
authors.lastname: Bulsara
authors.forename: Frank M
authors.initials: FM
authors.lastname: van Bockxmeer
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Powell
authors.forename: John P
authors.initials: JP
authors.lastname: Beilby
authors.forename: Gillian
authors.initials: G
authors.lastname: Arscott
authors.forename: Michael
authors.initials: M
authors.lastname: Le Page
authors.forename: Lyle J
authors.initials: LJ
authors.lastname: Palmer
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Davis
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Jones
authors.forename: Catherine S Y
authors.initials: CS
authors.lastname: Choong
mesh_terms: D000293:Adolescent; D000419:Albuminuria / Q000235:genetics*; D000808:Angiotensinogen / Q000235:genetics*; D001315:Australia; D002648:Child; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012084:Renin-Angiotensin System / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; D000808:Angiotensinogen