Relationship of angiotensin-converting enzyme gene polymorphism with nephropathy associated with Type 2 diabetes mellitus in Asian Indians

Movva, Sireesha; Alluri, Ravindra Varma; Komandur, S; Vattam, Kiran Kumar; Eppa, Kavitha; Mukkavali, Kamal Kiran; Mubigonda, Somashekhar; Saharia, S.S.; Shastry, Jandayala C.; Hasan, Qurratulain

doi:10.1016/j.jdiacomp.2006.07.001

Cited by 65 publications

(54 citation statements)

References 24 publications

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“…Therefore, we suggest that the genetic variation at the ACE locus as D/D variant in intron 16, contribute to an increased risk of nephropathy in T2DM patients, but not extent of DN severity (as the allelic or genotypic distribution was comparable between the two DN groups) in studied population. Our findings were in conformity with other studies [26][27][28][29][30][31] but not all [32,55,56]. This difference may possibly be due to different races, methods of quantitation and patient selection; as proteinuria in adults is a multifactorial condition frequently linked with diabetes, the issue of whether proteinuria is due to diabetes or some other etiology remains debatable, but there was no uncertainty in our group of patients on the role of T2DM in diabetic nephropathy constitution as we excluded the patients who had proteinuria/renal disorders before their diabetes was diagnosed, thus we confined our study to diabetic kidney diseases.…”

Section: Discussionsupporting

confidence: 94%

“…This polymorphism was associated with circulating ACE levels [23][24][25] and owing to its central role in the regulation of blood pressure, sodium metabolism and renal hemodynamics [16,17], it is reasonable to hypothesize that genetic variation of ACE I/D contributes to the development of DN and numerous studies have addressed the role of this polymorphism in the complex etiology of DN, albeit with conflicting results i.e. several studies have demonstrated [26][27][28][29][30][31] or refuted [32][33][34] the role of ACE D variant as candidates for the development of DN. The discrepant finding among studies is attributed to genetic and environmental heterogeneity among different populations.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

et al. 2013

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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: x 2 :8.87, 2 d.f. p = 0.0118; Rabari: x 2 :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 T2DM patients 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.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

et al. 2013

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“…In contrast, among Caucasians French, Turkish and Tunisian populations the ACE I/D polymorphism was not a marker for DN and renal prognosis of patients with T2DM (6,16,17,28). Also, among Iranians with Kurdish ethnic background ACE I/D polymorphism was not associated with the risk of microalbuminuria (10).…”

Section: Ace I/d Polymorphism: Onset and Progression Of Diabetic Nephmentioning

confidence: 89%

“…The role of ACE I/D polymorphism in the pathogenesis of DN has been investigated in various ethnic groups with inconsistent results (6,11,17,18). Ethnicity is one of the most important factors, which determines the role of ACE gene polymorphism in the susceptibility to DN.…”

Section: Ace I/d Polymorphism: Onset and Progression Of Diabetic Nephmentioning

confidence: 99%

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Rahimi¹

2012

J Nephropathol

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Implication for health policy/practice/research/medical education:The presence of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with highest systemic and renal ACE levels, compared with the lowest ACE activity in carriers of II genotype. Most studies confirmed that ACE I/D polymorphism is involved in the susceptibility to overt nephropathy with protective role of ACE II genotype against the disease in both type 1 and 2 diabetes mellitus. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Results:The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. Conclusions: In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.Review Article

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“…The ACE I/D gene was analyzed using polymerase chain reaction (PCR) and primers specified by Movva et al 6 The sequences of the primers were chosen such that they flank the targeted region of the genome on the intron 16 of ACE gene (17q23). The template DNA (0.…”

Section: Determination Of Ace I/d Polymorphismmentioning

confidence: 99%

Angiotensin-converting enzyme gene insertion/deletion polymorphism studies in Asian Indian pregnant women biochemically identifies gestational diabetes mellitus

Khan

Jahan

Hasan

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Introduction: Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy. Insertion/deletion (I/D) polymorphism of a 287 bp Alu repetitive sequence in intron 16 of the angiotensin-converting enzyme (ACE) gene has been widely investigated in Asian Indian populations with different ethnic origins. The present study examined possible association between I/D polymorphism of the ACE gene and GDM in Asian Indian pregnant women. Methods: A total of 200 pregnant women (100 GDM and 100 non-GDM) were recruited in this study and I/D polymorphism of a 287 bp Alu1 element inside intron 16 of the ACE gene was examined by polymerase chain reaction (PCR)-based gel electrophoresis. Result: The distribution of the variants like II, ID, and DD genotypes of ACE gene showed differences between normal GDM versus non-GDM subjects, and the frequency of the ID+ DD Vs II genotype was significant (p=0.0002) in the GDM group. Conclusion: ACE gene polymorphism was associated with GDM in Asian Indian pregnant women.

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Relationship of angiotensin-converting enzyme gene polymorphism with nephropathy associated with Type 2 diabetes mellitus in Asian Indians

Cited by 65 publications

References 24 publications

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Angiotensin-converting enzyme gene insertion/deletion polymorphism studies in Asian Indian pregnant women biochemically identifies gestational diabetes mellitus

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