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

Wyawahare, Mukta; Neelamegam, Revathy; Vilvanathan, Saranya; Rajendran, Senthilkumar; Ak, Das; Adithan, C

doi:10.1177/1179551417726779

Cited by 6 publications

(9 citation statements)

References 20 publications

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“…Recent research has been done to determine if the ACE Insertion/Deletion (I/D) polymorphism increases the likelihood that diabetic nephropathy would worsen. According to certain research done in Chinese and Indian populations, T2DM with DN is more likely to carry the ACE D allele;while other studies were conducted in Indian and Caucasian populations have found no association of either allele with the progression of nephropathy in T2DM [9,10] .…”

Section: Introductionmentioning

confidence: 95%

Association between Angiotensin Converting Enzyme Gene I/D and Promoter Polymorphisms and Diabetic Nephropathy in Type2 Diabetic Patients in Ismailia, Egypt

Hassan,

Tolba,

Leheta

et al. 2023

Preprint

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BACKGROUND: There is mounting evidence that the chronic activation of renal and systemic ACE, which results in the production of Angiotensin II, is a critical step in the pathogenesis of DN. Chronic ACE activation causes an increase in intraglomerular pressure, tissue damage, pro-inflammatory effects, and promotes fibrosis. AIM: The purpose of this study was to determine if ACE polymorphisms (I/D rs4646994 and promoter SNP, rs4292) and ACE level were related to the DN development in T2DM patients in the Egyptian community. PATIENTS AND METHODS: This study is designed as a case control study which enrolled 90 subjects divided into three groups: 30 diabetic patients without DN, 30 diabetic patients with DN and 30 healthy individuals as control group. We measured for each patient the following: serum creatinine, eGFR, ACR, lipid prolife, HbA1C, as well as serum ACE level. Genotyping of ACE I/D and promoter SNP, rs4292, polymorphisms in ACE gene were performed using conventional PCR assays. RESULTS: The laboratory data analysis revealed that the only variables across the trial groups that indicated a significant statistical difference were serum creatinine, eGFR, ACR, HDL-C, LDL-C, and HbA1c. Total cholesterol and triglycerides did not. Between the study groups, there was a substantial statistical difference in the level of serum ACE. In our population, the genotype and allele frequencies of the ACE I/D gene polymorphism varied considerably between research groups, suggesting that it may be a risk factor for DN. In comparison to individuals of the wild type (II), the (DD) genotype considerably raised the probability of progression to T2DM by about six times and of progression to DN by about ten folds. This study found that the ACE promoter rs4292 (C/T) polymorphism is a risk factor for developing DN. The (TT) genotype is associated with increased susceptibility to DN as it was higher in diabetic patients with nephropathy than the two other study groups. However, there was no statistically significant difference in the study variables among different genotypes subgroups. CONCLUSION:According to our research, the mutant alleles (T) of the ACE promoter rs4292 (C/T) polymorphism and the ACE I/D rs4646994 polymorphism may both be risk factors for DN in the Egyptian population.

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Section: Introductionmentioning

confidence: 95%

Association between Angiotensin Converting Enzyme Gene I/D and Promoter Polymorphisms and Diabetic Nephropathy in Type2 Diabetic Patients in Ismailia, Egypt

Hassan,

Tolba,

Leheta

et al. 2023

Preprint

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“…на примере бразильской популяции [25]. Не получено различий в распределении генотипов указанного гена у населения Южной Индии среди лиц с АУ и нормоальбуминурией [26]. С повышенным риском развития АУ установлена ассоциация полиморфизма гена AGTR1 у мужчин Дании, Финляндии, Франции и Швеции [27].…”

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Interrelation of cardiovascular risk factors with high albuminury among patients with arterial hypertension living in Mountain Shoriya

Мулерова¹,

Александровна²,

Filimonov

et al. 2019

Terapevticheskii arkhiv

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Aim: to evaluate the association of a complex of cardiovascular risk factors and genetic markers with the development of high albuminuria among patients with arterial hypertension in the population of Mountain Shoriya, taking into account ethnicity. Materials and methods. A clinical epidemiological study of a compactly residing population in remote areas of Mountain Shoria was carried out. 1409 people were examined [901 people - representatives of the indigenous nationality (Shorians), 508 people - representatives of non-indigenous nationality (90% of them are Caucasians)]. Hypertension was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). All patients underwent clinical, laboratory and instrumental investigation. To study the state of the kidneys, the concentration (the presence of elevated levels) of albumin (albuminuria) in the morning portion of urine by an immunoturbidimetric method was analyzed. Polymorphisms of genes ACE (I/D, rs4340), АGT (c.803T>C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A>G, Ser49Gly, rs1801252), ADRA2B (I/D, rs28365031), MTHFR (c.677С>Т, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using PCR. Results. In the group of shors with arterial hypertension, high albuminuria was associated with polymorphisms of the ACE genes (OR=2.05), ADRA2B (OR=6.00), elevated triglyceride level (OR=2.86), decreased index of cholesterol of high density lipoproteins (OR=5.57) and increased index of low density lipoproteins (OR=2.49); in the new population - with polymorphisms of the AGTR1 genes (OR=8.66), ADRA2B (OR=6.53), MTHFR (OR=7.16), obesity (OR=2.72), and abdominal obesity (OR=3.14). Conclusion. The primary predictors determining the development of high albuminuria among patients with arterial hypertension in both ethnic groups were genetic ones. In addition to them, non-genetic risk factors also contributed to the development of this organ damage to the kidneys: age and lipid metabolism disorders in representatives of indigenous nationality; age and abdominal obesity in the examined patients non-indigenous nationality.

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“…The ACE gene is made up of 21 kilobases on the long arm of human chromosome 17q23 forming three possible genotypes that is to say II, ID or DD. 11 These ACE genetic mutations have been considered to be putative mediators of renal disease, 9 although some studies are quite controversial. 6,11 Some studies have demonstrated an association between ACE (angiotensin-converting enzyme) insertion/deletion (I/ D) polymorphisms and various metabolic indicators in type 2 diabetes mellitus (T2D) patients, while others found otherwise.…”

Section: Introductionmentioning

confidence: 99%

“…11 These ACE genetic mutations have been considered to be putative mediators of renal disease, 9 although some studies are quite controversial. 6,11 Some studies have demonstrated an association between ACE (angiotensin-converting enzyme) insertion/deletion (I/ D) polymorphisms and various metabolic indicators in type 2 diabetes mellitus (T2D) patients, while others found otherwise. A study found an association between these polymorphisms with coronary heart disease and dyslipidemia in T2D patients.…”

Section: Introductionmentioning

confidence: 99%

Distribution of the ACE Gene Polymorphisms in Type 2 Diabetes Mellitus Patients, Their Associations with Nephropathy Biomarkers and Metabolic Indicators at a Tertiary Hospital in Uganda

Kiconco,

Kalyesubula,

Kiwanuka

2024

DMSO

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Purpose We aimed at determining the distribution of the ACE insertion/deletion gene polymorphisms among type 2 diabetic patients and their association with the nephropathy biomarkers and the metabolic indicators. Patients and Methods Data were collected from 237 adult type 2 diabetes mellitus patients receiving healthcare at the diabetic clinic of Mbarara Regional Referral Hospital. Peripheral blood genomic DNA was amplified using a conventional PCR technique and analyzed for the ACE homozygous forms of the insertion (II), deletion (DD) and heterozygous insertion deletion (ID) genotypes as well as their respective allele counts. Biomarkers of nephropathy were analyzed on a Beckman coulter AU480 chemistry analyzer using system compatible reagents. Results Majority of the participants were older persons (Median = 57, IQR = 49–64) and female 171 (72.2%). Most of them had the Deletion allele 198 (83.5%) and DD genotype 116 (48.9%). At multivariate logistic regression, the nephropathy biomarkers that is microalbuminuria, serum creatinine, urea, eGFR and electrolytes had no association with the ACE I/D alleles or genotypes (p > 0.05). On the other hand, selected metabolic indicators had a positive relationship. The insertion allele was associated with increasing glycated hemoglobin (OR = 1.082, p = 0.019) and decreasing serum glucose levels (OR = 0.891, p = 0.001). Deletion allele was associated with decreasing glycated hemoglobin (OR = 0.924, p = 0.047) and increasing serum glucose levels (OR = 1.208, p = 0.001). ACE II genotype was associated with decreasing serum glucose levels (OR = 0.873, p = 0.029). ACE DD genotype was associated with decreasing glycated hemoglobin (OR = 0.917, p = 0.010) and increasing serum glucose levels (OR = 1.132, p = 0.001). ACE ID genotype was associated with increasing glycated hemoglobin (OR = 1.077, p = 0.022), triglyceride levels (OR = 1.316, p = 0.031) and decreasing serum glucose levels (OR = 0.933, p = 0.038). Conclusion The presence or absence of the ACE I/D alleles and genotypes affects the ultimate increase or decrease in the serum glucose, glycated hemoglobin and triglyceride levels. Although there was no significant association between the biomarkers of nephropathy and the ACE I/D alleles or genotypes, the above implicated metabolic indicators should be included in healthcare guidelines used when attending to type 2 diabetic patients.

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

Cited by 6 publications

References 20 publications

Association between Angiotensin Converting Enzyme Gene I/D and Promoter Polymorphisms and Diabetic Nephropathy in Type2 Diabetic Patients in Ismailia, Egypt

Association between Angiotensin Converting Enzyme Gene I/D and Promoter Polymorphisms and Diabetic Nephropathy in Type2 Diabetic Patients in Ismailia, Egypt

Interrelation of cardiovascular risk factors with high albuminury among patients with arterial hypertension living in Mountain Shoriya

Distribution of the ACE Gene Polymorphisms in Type 2 Diabetes Mellitus Patients, Their Associations with Nephropathy Biomarkers and Metabolic Indicators at a Tertiary Hospital in Uganda

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