Angiotensinogen gene T235 variant: A marker for the development of persistent microalbuminuria in children and adolescents with type 1 diabetes mellitus

Authors

Patricia H. Gallego
Neil Shephard
Max K. Bulsara, University of Notre Dame AustraliaFollow
Frank M. van BockxmeerFollow
Brenda L. Powell
John P. Beilby
Gillian Arscott
Michael Le Page
Lyle J. Palmer
Elizabeth A. Davis
Timothy W. Jones
Catherine S Y Choong

Publication Details

Gallego, P. H., Shephard, N., Bulsara, M. K., van Bockxmeer, F. M., Powell, B. L., Beilby, J. P., et al. (2008). Angiotensinogen gene T235 variant: A marker for the development of persistent microalbuminuria in children and adolescents with type 1 diabetes mellitus. Journal of Diabetes and Its Complications, 22(3), 191–198. doi:10.1016/j.jdiacomp.2007.03.003

Abstract

Aim: 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 z20 and b200 Ag/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 (logrank 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).

Interpretation: Our findings suggest that RAS gene polymorphism at AGT M235T is a strong predictor for early MA in young T1DM subjects.

Keywords

peer-reviewed