Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region
Genetic polymorphism as described with angiotensin-
converting enzyme gene has been proposed as a
putative mediator of diabetic nephropathy. We substantiate
the hypothesis that genetic variants of the ACE have significant
impacts on diabetic nephropathy. To assess the possible
association between the three ACE polymorphic variants and
DN in an ethnically homogeneous type 2 diabetic population
from Kutch region. A 287-bp insertion/deletion polymorphism
in intron 16 of the ACE gene was examined by polymerase
chain reaction using a case–control approach
conducted with 309 unrelated type 2 diabetic patients of
Kutch origin (159 Ahir and 150 Rabari, with [10 years
duration of T2DM). Of the patients, 143 had nephropathy
{AER[30 mg/day (Ahir, n:73 and Rabari, n:70)} and were
considered as cases; all others {n:166 (86 Ahir and 80 Rabari)}
were normoalbuminuric (AER\30 mg/day) and were
treated as controls. Suitable descriptive statistics was used for
different variables. Genotype frequencies in all groups were
all in accordance with the Hardy–Weinberg equilibrium.
Genotypic distribution was significantly different between
cases and controls (Ahir: x2 :8.87, 2 d.f. p = 0.0118; Rabari:
x2 :11.01, 2 d.f. p = 0.0041). Multivariate logistic regression
analysis revealed that DD genotype was a significant and
strongest independent predictor of microalbuminuria (Ahir:
p = 0.0362, OR = 2.65, 95 % CI 1.89–6.36; Rabari:
p = 0.024, OR = 2.81, 95 % CI 1.9–6.65). However, it did
not independently change the odds of having macroalbuminuria
versus microalbuminuria. Analysis of the association under various genetic models revealed that ACE I/D polymorphic
variant contribute to DN susceptibility under
recessive mode only. Genetic variation at the ACE locus as
D/D variant in intron 16, contribute to an increased risk of
nephropathy in T2DMpatients but not extent of DN severity,
and thus this polymorphism might be considered as genetic
risk factors for DN among patients with type 2 diabetes.
converting enzyme gene has been proposed as a
putative mediator of diabetic nephropathy. We substantiate
the hypothesis that genetic variants of the ACE have significant
impacts on diabetic nephropathy. To assess the possible
association between the three ACE polymorphic variants and
DN in an ethnically homogeneous type 2 diabetic population
from Kutch region. A 287-bp insertion/deletion polymorphism
in intron 16 of the ACE gene was examined by polymerase
chain reaction using a case–control approach
conducted with 309 unrelated type 2 diabetic patients of
Kutch origin (159 Ahir and 150 Rabari, with [10 years
duration of T2DM). Of the patients, 143 had nephropathy
{AER[30 mg/day (Ahir, n:73 and Rabari, n:70)} and were
considered as cases; all others {n:166 (86 Ahir and 80 Rabari)}
were normoalbuminuric (AER\30 mg/day) and were
treated as controls. Suitable descriptive statistics was used for
different variables. Genotype frequencies in all groups were
all in accordance with the Hardy–Weinberg equilibrium.
Genotypic distribution was significantly different between
cases and controls (Ahir: x2 :8.87, 2 d.f. p = 0.0118; Rabari:
x2 :11.01, 2 d.f. p = 0.0041). Multivariate logistic regression
analysis revealed that DD genotype was a significant and
strongest independent predictor of microalbuminuria (Ahir:
p = 0.0362, OR = 2.65, 95 % CI 1.89–6.36; Rabari:
p = 0.024, OR = 2.81, 95 % CI 1.9–6.65). However, it did
not independently change the odds of having macroalbuminuria
versus microalbuminuria. Analysis of the association under various genetic models revealed that ACE I/D polymorphic
variant contribute to DN susceptibility under
recessive mode only. Genetic variation at the ACE locus as
D/D variant in intron 16, contribute to an increased risk of
nephropathy in T2DMpatients but not extent of DN severity,
and thus this polymorphism might be considered as genetic
risk factors for DN among patients with type 2 diabetes.