Angiotensin converting enzyme (ACE) gene polymorphism increases the susceptibility of diabetic nephropathy in Western Indian Type 2 diabetic patients

Introduction: The insertion/deletion (I/D) polymorphism of 287 bp Alu repeat sequence in intron 16 of Angiotensin Converting Enzyme (ACE) gene resulting in three genotypes I/D, D/D and I/I. ACE gene expression is associated with ACE levels in cells and in the plasma. It indicated that the polymorphism may modulate the expression of the ACE gene. The D/D genotype is believed to confer deleterious effect to many pathogenesis, also, it might be a cause-effect for type 2 diabetic nephropathy (T2DN). In this study, we evaluated the frequency of the different genotypes of ACE gene and investigated if there is an association between ACE gene polymorphism and T2DN by comparing the genotypes results of T2DN patients to healthy control, Type 2 diabetes mellitus (T2DM) and nephropathy patients in Gaza Strip. Methodology: The study included 170 subjects, consisting of 43 T2DM patients undergoing dialysis "T2DN" compared to 41 T2DM patients who were not undergoing dialysis, 43 patients undergoing dialysis without T2DM and 43 healthy individuals. Blood samples were collected in EDTA tubes for DNA extraction. Polymerase Chain Reaction (PCR) was used to detect ACE gene polymorphism. All subjects were asked to fill the questionnaire interview. Results and Conclusion: The initial results showed that there is no statistically significant association between ACE genotypes and T2DN, also between the T2DM and nephropathy when compared to the healthy control (p> 0.05). The (D/D) genotype was the most frequent in all study groups. Moreover, no association was observed between ACE genotypes and gender, diabetic nephropathy, nephropathy, diabetes, hypertension, obesity and various other diabetes complications.

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Association of Angiotensin-Converting Enzyme Gene Polymorphisms and Nephropathy in Diabetic Patients at a Tertiary Care Centre in South India

Clinical Medicine Insights Endocrinology and Diabetes ◽

10.1177/1179551417726779 ◽

2017 ◽

Vol 10 ◽

pp. 117955141772677

Author(s):

Mukta Wyawahare ◽

Revathy Neelamegam ◽

Saranya Vilvanathan ◽

R Soundravally ◽

AK Das ◽

...

Keyword(s):

Gene Polymorphism ◽

Angiotensin Converting Enzyme ◽

Tertiary Care ◽

Diabetic Patients ◽

Genotype Distribution ◽

Converting Enzyme ◽

Ace Gene ◽

Ace Gene Polymorphism ◽

Group 2

Background: Genetic polymorphisms of the angiotensin-renin pathway have been thought to influence the development of diabetic nephropathy. However, there are conflicting results regarding this association in previous studies on populations with varying ethnicity. Aims: Primary aim was to compare the frequency of distribution of angiotensin-converting enzyme ( ACE) gene (insertion/deletion [I/D]) polymorphism in Tamilian Indian type 2 diabetic individuals with and without microalbuminuria. Secondary objective was to compare the frequency of distribution of the 3 genotypes in diabetic patients with urinary albumin/creatinine ratio (ACR) < 30 mg/dL, urinary ACR = 30 to 300 mg/dL, and urinary ACR > 300 mg/dL. Methods: A total of 179 consecutive diabetic individuals between 40 and 70 years, from Puducherry and Tamilnadu of Dravidian descent participated in the study conducted from 2012 to 2014. Inclusion criteria were as follows: age ≥ 40 years and duration of type 2 diabetes mellitus for ≥5 years. Patients were divided into 2 groups based on ACR values. Group 1 consisted of 50 individuals with urinary ACR < 30 mg/g of creatinine, and group 2 consisted of 129 individuals with urinary ACR > 30 mg/g. Angiotensin I–converting enzyme ( ACE) gene polymorphism was determined by allele-specific polymerase chain reaction method using a primer pair flanking the polymorphic region of its intron 16. Furthermore, group 2 patients were subdivided into those with urinary ACR = 30 to 300 mg/g of creatinine and those with urinary ACR > 300 mg/g of creatinine, and distribution of ACE gene polymorphism was compared in the three groups. Statistics: Statistical analysis was done using SPSS version 17.0. Independent Student t test was used to compare mean values between the 2 groups. Odds ratio was calculated for testing association between ACE gene (I/D) polymorphism and presence of microalbuminuria. P < .05 was considered significant. Comparison of ACE genotypes among 3 groups of patients (ACR < 30 mg/g, ACR = 30-300 mg/g, and ACR > 300 mg/g) was done using 1-way analysis of variance with Bonferroni multiple comparison test as post hoc analysis. Conclusions: Heterozygous I/D genotype was more frequent in the study population (45.8%) than the other genotypes. There was no difference in the genotype distribution in patients with varying levels of albuminuria.

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Angiotensin-converting enzyme gene polymorphism and microvascular complications in Turkish type 2 diabetic patients

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(01)00257-1 ◽

2001 ◽

Vol 54 (2) ◽

pp. 95-104 ◽

Cited By ~ 23

Author(s):

Mustafa Araz ◽

Necat Yilmaz ◽

Kivanc Güngör ◽

Vahap Okan ◽

Yalcin Kepekci ◽

...

Keyword(s):

Gene Polymorphism ◽

Angiotensin Converting Enzyme ◽

Microvascular Complications ◽

Diabetic Patients ◽

Angiotensin Converting Enzyme Gene ◽

Converting Enzyme ◽

Type 2 Diabetic Patients ◽

Enzyme Gene ◽

Type 2 Diabetic

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ACE gene polymorphism and serum ACE level with Progression of Nephropathy in Type 2 Diabetic Patients

JOURNAL OF ADVANCES IN CHEMISTRY ◽

10.24297/jac.v9i3.1009 ◽

2013 ◽

Vol 9 (3) ◽

pp. 2023-2032

Author(s):

Olfat Gamil Shaker ◽

Manal Fouad Ismail ◽

Esmat Ashour ◽

Heba Mourad Yousif ◽

Mie Afify ◽

...

Keyword(s):

Gene Polymorphism ◽

Strong Association ◽

Elevated Serum ◽

Renin Angiotensin System ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Ace Gene ◽

Ace Gene Polymorphism ◽

Type 2 Diabetic

Background. One of the most common complications of diabetes mellitus (DM) is diabetic nephropathy (DN). Angiotensin- converting enzyme (ACE) gene was the first candidate gene of renin-angiotensin system (RAS) for predisposition to DN.Objective. Investigation whether the ACE insertion/deletion (I/D) polymorphism is associated with Egyptian type 2 diabetic patients (T2DM) with nephropathy. In addition, the study investigated the relationship between variants of ACE I/D gene polymorphism and serum ACE level and the progression of nephropathy in Egyptian T2DM patients.Methods. A total of 85 T2DM patients (45 with nephropathy and 40 without nephropathy) besides 45 healthy (non-diabetic) age-matched subjects were recruited in this study for comparison. The (I/D) polymorphism of the ACE gene was investigated using PCR and serum ACE levels were determined using ELISA.Results. The frequency of ACE DD genotype and D allele was significantly higher in DN patients when compared to control healthy subjects and diabetic patients without nephropathy. In addition our results showed a significant association between DD genotype of ACE gene and elevated serum ACE level.Conclusion. The present study showing a strong association between the D allele and/or DD homozygous of ACE gene and diabetic patients developed nephropathy. In addition, individuals with D allele have higher levels of serum ACE compared to those having I allele. ACE gene polymorphism and serum ACE level may serve as a susceptibility biomarker for nephropathy in type 2 diabetic patients.

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