Influence of genetic variability at the ACE locus in intron 16 on Diabetic Nephropathy in T1DM patients.

ABSTRACT

Background: Diallelic [insertion/deletion (I/D)] polymorphism in the angiotensin-converting enzyme (ACE) gene has been reported inconsistently as being associated with risk of diabetic nephropathy (DN). Objective: To examine the three ACE poly-morphic variants in intron 16 for a possible role in modulating DN in T1DM patients from Kutch region, Gujarat. Design and setting: I/D polymorphism in intron 16 of the ACE gene was examined in a case-control group (280 participants with T1DM, case participants n=138; control participants n=142) for association with nephropathy. All recruited individuals were carefully phenotyped and genotyping was performed using polymerase chain reaction and gel electrophoresis methods. Suitable descriptive statistics was used for different variables. Results: No departure from Hardy-Weinberg equilibrium was observed in cases or controls. Genetic polymorphism at the ACE locus in intron 16 were significantly associated with nephropathy when analyzed either by genotype or allele frequencies and D/D variant were significantly (p=0.0002) associated with nephropathy at the 5% level. In multivariate analysis, D/D variant had an independent and strongest influence on the micro-albumin excretion (p=0.002, OR=2.11, 95% CI=1.26– 4.48). However, it did not independently change the odds of having macroalbuminuria versus microalbuminuria. Conclusion: Genotype-associated differences in ACE in intron 16, have functional consequences in genetic susceptibility to diabetic nephropathy in a population with T1DM, and thus represent a potential DN genetic susceptibility locus worthy of replication.