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