Angiotensin converting enzyme gene polymorphism in type II diabetics with nephropathy

Naresh, V.; Reddy, Aravinda; Sivaramakrishna, G.; Sarma, Potukuchi Venkata Gurunadha Krishna; Vardhan, RV; Kumar, V Siva

doi:10.4103/0971-4065.59335

Cited by 21 publications

(9 citation statements)

References 13 publications

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“…In support of a genetic etiology for subtype 1 phenotype manifestation, the ACE gene, which encodes angiotensin I converting enzyme and was specifically associated with this cohort (Table 3A and Fig. 2), has been implicated in diabetic nephropathy (52, 53) and also in platelet aggregation (53). Accordingly, this association could reasonably suggest a mechanism to explain the lower platelet counts observed in subtype 1 patients (54).…”

Section: Discussionmentioning

confidence: 69%

Identification of type 2 diabetes subgroups through topological analysis of patient similarity

et al. 2015

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Type 2 diabetes (T2D) is a heterogeneous complex disease affecting more than 29 million Americans alone with a rising prevalence trending toward steady increases in the coming decades. Thus, there is a pressing clinical need to improve early prevention and clinical management of T2D and its complications. Clinicians have understood that patients who carry the T2D diagnosis have a variety of phenotypes and susceptibilities to diabetes-related complications. We used a precision medicine approach to characterize the complexity of T2D patient populations based on high-dimensional electronic medical records (EMRs) and genotype data from 11,210 individuals. We successfully identified three distinct subgroups of T2D from topology-based patient-patient networks. Subtype 1 was characterized by T2D complications diabetic nephropathy and diabetic retinopathy; subtype 2 was enriched for cancer malignancy and cardiovascular diseases; and subtype 3 was associated most strongly with cardiovascular diseases, neurological diseases, allergies, and HIV infections. We performed a genetic association analysis of the emergent T2D subtypes to identify subtype-specific genetic markers and identified 1279, 1227, and 1338 single-nucleotide polymorphisms (SNPs) that mapped to 425, 322, and 437 unique genes specific to subtypes 1, 2, and 3, respectively. By assessing the human disease–SNP association for each subtype, the enriched phenotypes and biological functions at the gene level for each subtype matched with the disease comorbidities and clinical differences that we identified through EMRs. Our approach demonstrates the utility of applying the precision medicine paradigm in T2D and the promise of extending the approach to the study of other complex, multi-factorial diseases.

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Section: Discussionmentioning

confidence: 69%

Identification of type 2 diabetes subgroups through topological analysis of patient similarity

et al. 2015

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“…The association of ACE I/D polymorphism with T2DM risk and related renal and cardiovascular complications has been extensively studied throughout all the major ethnic groups but with highly inconsistent findings. Whereas some have found that the D allele is more common in T2DM and related complications in Tunisian [ 16 ], Indian [ 17 ], and Iranian populations [ 18 ], others have demonstrated no association of either allele with T2DM or related cardiovascular and renal disease in Malay and Indonesians [ 19 – 21 ]. The association between these polymorphisms and the ACE gene is similarly discrepant between its association with hypertension in the Japanese [ 22 ] and its nonassociation in the Chinese [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Angiotensin Converting Enzyme Insertion-Deletion Polymorphism with Hypertension in Emiratis with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status

et al. 2015

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The association of Angiotensin Converting Enzyme (ACE) insertion-deletion (I/D) polymorphism with Type 2 Diabetes Mellitus (T2DM) and hypertension has been extensively studied throughout various ethnic populations but largely with inconsistent findings. We investigated these associations in Emirati population and their interaction with obesity status. Saliva samples were collected from a total of 564 Emiratis (277 T2DM and 297 healthy). DNA was extracted and the samples were genotyped for ACE I/D polymorphism by a PCR based method followed by gel electrophoresis. Upon evaluation of the ACE I/D polymorphism amongst all T2DM, hypertensive patients, and respective controls regardless of obesity status, ACE DD genotype was not found to be associated with either T2DM [odds ratio (OR) = 1.34, p = 0.086] or hypertension [odd ratio (OR) = 1.02, p = 0.93]. When the genetic variants amongst the nonobese and obese population were analyzed separately, the risk genotype ACE DD conferred significantly increased risk of hypertension in nonobese population [odds ratio (OR) = 1.80, p = 0.02] but was found to be protective against the hypertension in the obese group ((OR) = 0.54, p = 0.01). However, there was no effect of obesity status on the association of ACE genotypes with T2DM. The risk of hypertension associated with ACE DD is modulated by obesity status and hence future genetic association studies should take obesity into account for the interpretation of data. We also confirmed that ACE I/D polymorphism is not associated with T2DM risk in Emirati population.

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“… 7 However, our results are in contrast to previous studies from South India which reported an association of D/D polymorphism with nephropathy in type 2 diabetes subjects. 19 , 20 However, number of participants studied was small in these studies. Another study from Gujarat also found microalbuminuria to be more prevalent in those patients with insulin-dependent diabetes mellitus who had D/D polymorphism.…”

Section: Discussionmentioning

confidence: 96%

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

Wyawahare

Neelamegam

Vilvanathan

et al. 2017

Clin Med Insights Endocrinol Diabetes

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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 in type II diabetics with nephropathy

Cited by 21 publications

References 13 publications

Identification of type 2 diabetes subgroups through topological analysis of patient similarity

Identification of type 2 diabetes subgroups through topological analysis of patient similarity

Association of Angiotensin Converting Enzyme Insertion-Deletion Polymorphism with Hypertension in Emiratis with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status

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

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