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Diabetes & Obesity International Journal Research Article 25 min read

Association of Angiotensin II Type I Receptor (AGTR1) Gene Polymorphism and Type 2 Diabetes & Nephropathy among the Eastern Indian Bengali Patients

Halder K and Purkait P*
* Corresponding author
ISSN: 2574-7770  10.23880/doij-16000224  Received: April 01, 2020  Published: April 24, 2020
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Keywords
Angiotensin II type I receptor Type 2 diabetes Nephropathy Eastern Indian Bengali
Abstract

Genetic polymorphisms of the angiotensin II type I receptor (AGTR1), has been reported to be the most probable candidate genes for hypertension, diabetes and complication of diabetes. Ethnic differences in the frequencies of these gene genotypes have also been reported. As there is no data available for AGTR1 polymorphism and T2DM in the Bengali population, it’s our attempt to fill the scientific gap. To investigate whether the angiotensin II type I receptor gene A1166C (rs5186) polymorphism is associated with a risk of type 2 diabetes and nephropathy in Indian Bengali patients, in a case-control study, the AGTR1 gene (rs5186; A1166C) was examined in type 2 diabetic patients with and without nephropathy (T2DM: N=246; T2DNH: N= 168) and normal control (N=304) participants and genotyped using PCR-RFLP methods. Result of Fisher exact test for allelic association of SNP rs5186 exhibits significant difference in the allele frequencies between the control and T2DM groups p= 0.0308). It is observed through the 4 genotypic model tests that additive model predicted significant association than basic genotype, dominant and recessive models and shows significant difference between CON vs. T2DM groups (p = 0.038). The present study reveals that the A1166C polymorphism (rs5186) of AGTR1 has a positive association with T2DM. This polymorphism with C allele may contribute to diabetic complication, nephropathy development particularly in T2DM patients.

Introduction

Type 2 Diabetes Mellitus (T2DM) constitutes the major mass of diabetes and India is the “Diabetes Capital of the World” with 69.2 million Indians having diabetes and with an estimated  72 million cases  in 2017 [1, 2] with every fifth diabetic in the world being an Indian. Nephropathy is a complication of diabetes and is related to the damage or disease of kidney. Diabetic nephropathy is impairment to the kidney caused by the hyperglycemia and characterized by consistent proteinuria (>300 mg/ 24 h) convoyed by increased arterial blood pressure and steady decline in renal function. In severe cases kidney can be failure. The kidneys filter waste from blood through its capillaries. Diabetes result of high blood sugar can destroy these tiny blood vessels. Renal failure or kidney disease in diabetes is intervened by various biochemical pathways such as renin-angiotensin-aldosterone system (RAAS) [3, 4], aldose reductase-polyol [5], di-acyl glycerol-protein kinase C [6], hexosamine pathway [7] and advanced glycosylation end products (AGE) [8, 9]. The renin- angiotensin-aldosterone system (RAAS) actually provides a signal transduction mechanism for regulating body’s blood pressure and water balance. When an individual confronted with low blood pressure or certain nerve impulse such as stressful situation, the kidneys release an enzyme known as renin. This triggers a signal transduction pathway: renin cleaves the circulating protein angiotensinogen to produce angiotensin I, which is later converted to angiotensin II by another enzyme angiotensin converting enzyme (ACE). Angiotensin II causes blood vessels to compress, which results in high blood pressure. It also stimulates the secretion of the water retaining hormone vasopressin in the pituitary gland as well as the release of adrenaline, noradrenaline and aldosterone in the adrenal gland [10, 11, 12, 13].

The biological effects of angiotensin II are mediated via the angiotensin II receptor. By the help of ligand binding experiments two subtypes of cell surface receptors have been identified (AT1 & AT2) and are classified to the G-protein coupled receptor super family, which has seven transmembrane spanning domain[14]. In humans, the AT1 receptor is present predominantly in vascular smooth muscle cells, and the AT2 receptor is present in the uterus, brain and adrenal medulla [15, 16]. Both subtypes are also expressed in the adrenal cortex and kidney [17]. But most of the physiologic and pathphysiologic signals of Ang II, such as vasoconstriction, aldosterone release, stimulation of tubular transport, renal sodium reabsorption, proinflmmatory effects and growth stimulatory actions are transduced by AGTR1 receptors [18]. The AGTR1 gene extents >55 kilo bases (kb) on chromosome 3q22 and comprises of five exons, four of which are untranslated and alternatively spliced [19]. It has been found that AGTR1 is highly polymorphic [20, 21, 22, 23] but particularly rs5186 (A1166C) polymorphism of the AGTR1 gene, which was primarily identified by Bonnardeaux et al., a substitution of adenine (A) by cytosine (C) at position 1166, positioned at the 5’ end of the 3’ un-translated region of the gene, is the best evaluated [20] . Except this A1166C polymorphism, few other DNA polymorphisms have no significant impact on hypertension, diabetic nephropathy or myocardial infarction [20, 21, 22].

The renin-angiotensin-aldosterone system regulates not merely blood pressure but also the internal pressure of the glomerulus, and hypertension, which is an independent risk factor of diabetic nephropathy. The RAAS has been implicated in the pathogenesis of progressive renal disease [24, 25], diabetic renal complications [26] and seem to be especially relevant both biologically and clinically to renal disease [27, 28]. Therefore polymorphisms of RAAS candidate genes such as AGT, ACE, REN and AGTR1 are closely related to the progression of DN [13, 29, 30, 31, 32, 33]. Several studies suggest that the AGTR1 receptor might be involved in DN, type2 diabetes [21, 34, 35, 36], though many other investigator did not find any such relation between polymorphism of AGTR1 gene and diabetes as well as diabetic nephropathy [37, 38, 39]. Erstwhile we have identified that RAAS gene candidates ACE, AGT, CYP11B2, REN polymorphisms are significantly associated with type2 diabetes, hypertension, DN respectively, in eastern Indian Bengali population and western Indian Mewari population [13, 33, 40, 41].

Due to controversial results about the role of AGTR1 gene locus in diabetes, DN and the lack of information in this regard in Bengali population the aim of our present study was to scrutinize the role of AGTR1, in the development of DN in type 2 diabetes mellitus in Bengali population.

Materials and Methods

Study Patients

Recruitment of patients and study design describe elsewhere [13, 33]. Patients were recruited from registered patients list of two participating medical institutions of Kolkata city, West Bengal. A total of 718 age and sex matched individuals were participated in the present study, out of which 55.40% (n=398) male and 44.60% (n= 320) female. The study included 304 healthy control (CON: Male = 180; Female = 124), 246 type 2 diabetes patients without nephropathy (T2DM: Male = 128; Female = 118 )and 168 type 2 diabetic nephropathy patients on hemodialysis (T2DNH: Male = 90 ; Female = 78 ). The identification of Type 2 diabetic and nephropathy patients was based on physician’s recommendation or registered patient for dialysis. The unrelated controls were randomly selected and recruited from local community centres. A standardized protocol was implemented to obtain detailed medical history and data from each of the study participants. Ethical committee clearance was obtained from the medical institutions prior to the recruitment of subjects in this study. An informed consent was obtained from all the participants prior to their recruitment for the study.

Genotyping

Genomic DNA was prepared from fresh whole blood by using the conventional phenol-chloroform extraction method followed by ethanol precipitation [42]. DNA working dilutions (100μl) were prepared at a concentration of 50ng/ μl by dissolving required amount of stock DNA sample in TE buffer. After preparation of working dilutions the uniformity of the samples were checked by performing electrophoresis on a 1% agarose gel. In this study, previously published primers were used for the PCR based detections of SNPs [30, 40]. PCR amplification was performed in a final volume of 10μL reaction mixture containing 50ng of genomic DNA, 20 pmol of each primer, 10X Taq PCR buffer, 25 mM MgCl2, 100 mM of each dNTPs and 0.5 U/uL of Red Taq polymerase. PCR amplification was performed in a DNA thermo cycler (Bio- Rad). The DNA was amplified for 35 cycles with denaturation at 94°C for 1 min, annealing at 61°C for 1:30 min and extension at 72°C for 1:30 min and final extension 72°C for 10 min. The PCR products were checked by 2% agarose gel electrophoresis with ethidium bromide staining and directly visualized in UV light. Only those PCR products that had a single amplification product with no evidence of non-specific amplification were used for PCR-RFLP, details about the PCR- RFLP of AGTR1 gene described in our previous article [43].

Statistical Analysis

Allele frequencies were calculated for all the SNPs and were tested for Hardy-Weinberg equilibrium (HWE) and allelic association with the disease (Chi-Square test / Fisher exact test). Allelic and genotype association with the phenotypes was tested under different genetic models for both quantitative and qualitative traits by regression analysis and Fisher Model Test. Allele frequencies were calculated for the SNPs and tested for Hardy-Weinberg equilibrium (HWE) and allelic association with disease (Fisher exact test, logistic regression and Fisher model tests) using PLINK software [44]. For comparing the allelic distributions between study groups, the odds ratio (OR) with 95% confidence interval (CI) were also calculated. Quantitative data were analyzed using SPSS Version 16.0 (SPSS Inc., Chicago,IL, USA), were expressed as Mean ± SD and ANOVA test were used to determine differences in means and significance levels. A level of p <0.05 was assumed statistically significant.

Results

Genotype and Allele Frequency

Distribution of study groups based on genotype of AGTR1 gene polymorphism presented in Table 1. CC genotype were found among only 10 patients, out of which 8 patients are belongs to T2DM group and only 2 patients in T2DNH group.

The SNP rs5186 is an established polymorphism of the AGTR1 gene on chromosome 3: 148459988. It occurred in three forms, wild type homozygous AA, heterozygous AC and mutant homozygous CC (Figure 1). Genotype distribution of this polymorphism is presented in Table 2 and statistical analyses are given in Table 3 to Table 6. . The results of Hardy-Weinberg Equilibrium (HWE) test for rs5186 (A>C) of AGTR1 gene among the present study groups are presented in Table 3. From the HWE test it is found that the SNP rs5186 is not in Hardy-Weinberg equilibrium among T2D and T2DM groups, whereas Control and T2DNH groups maintain the Hardy-Weinberg Equilibrium.

Result of Fisher exact test for allelic association of SNPrs5186 (A>C) of AGTR1 gene among the study groups is presented in Table 4. The results exhibit no significant difference in the allele frequencies of the SNP between the control and T2D groups. However, significant differences are observed between CON vs. T2DM (χ2= 4.664, OR= 1.593, p= 0.0308) and T2DM vs. T2DNH (χ2= 3.967, OR= 0.5928, p=0.04639) groups.

The associations were further verified through 4 genotypic model tests (Fisher model test) to confirm which of these models predict best associations between the study groups and the results are presented in table 5. It is observed through the analyses that additive model predicted significant association than basic genotype, dominant and recessive models and shows significant difference between CON vs. T2DM groups (TREND, χ2 =4.269, p = 0.03882).

The mean values of quantitative variables, among study group based on AGTR1 gene genotype are presented in Table 6. The mean values of weight, BMI, triglyceride, total protein, globulin were significantly higher among the CC genotype group compared to AA and AC genotype groups of AGTR1 gene. The CC genotype individuals are relatively shorter while AA and AC genotype individuals are taller. Mean value of blood glucose comparatively higher among the CC genotype group, although not at significant level.

Comparison of Allele Frequency of AGTR1 Gene Variant Rs5186 with World Population

The allele frequency of the variant is calculated in the Indian Bengali population as well as in the World populations to check the utility of the SNP as a marker in our population as well as in the World populations (Table 7). The allele frequency of the rs5186 has been illustrated by the column graph in Figure 2. It is evident that the minor allele frequency is quite low in African population (YRI) where the ‘C’ allele shows a low frequency of 0.011, which is yielding a very low heterozygosity. The ancestral allele (A) frequency is quite high in all populations except in the European population and the lowest frequency among IBS population (0.679). Although European and American populations show quit higher frequency of minor allele, the two Mongoloid Asian populations CHB and JPT show similar profile, whereas the present study Indian Bengali population shows profile similar to the all Asian (ASN) and CHS populations.

Figure 1: Ethedium bromide stained 2.5% agarose gel shows digested products for AGTR1 A1166C polymorphism(rs5186) by HpyF3I (DdeI) restriction enzyme . Fragments for allele ‘A’ = 536 bp and 90 bp ; allele ‘C ‘= 417 bp, 119 bp, and 90bp. Lane 1: DNA marker.; Lane 2,3,6 : Genotype AA : 2 Fragments of 536 bp and 90 bp ; Lane 4: Undigested PCR product ; Lane 5: Genotype AC : 4 fragments of 536 bp, 417 bp , 119 bp and 90 bp.
Click to enlarge
Figure 1: Ethedium bromide stained 2.5% agarose gel shows digested products for AGTR1 A1166C polymorphism(rs5186) by HpyF3I (DdeI) restriction enzyme . Fragments for allele ‘A’ = 536 bp and 90 bp ; allele ‘C ‘= 417 bp, 119 bp, and 90bp. Lane 1: DNA marker.; Lane 2,3,6 : Genotype AA : 2 Fragments of 536 bp and 90 bp ; Lane 4: Undigested PCR product ; Lane 5: Genotype AC : 4 fragments of 536 bp, 417 bp , 119 bp and 90 bp.

Figure 1: Ethedium bromide stained 2.5% agarose gel shows digested products for AGTR1 A1166C polymorphism(rs5186) by HpyF3I (DdeI) restriction enzyme . Fragments for allele ‘A’ = 536 bp and 90 bp ; allele ‘C ‘= 417 bp, 119 bp, and 90bp. Lane 1: DNA marker.; Lane 2,3,6 : Genotype AA : 2 Fragments of 536 bp and 90 bp ; Lane 4: Undigested PCR product ; Lane 5: Genotype AC : 4 fragments of 536 bp, 417 bp , 119 bp and 90 bp.

AGTR1 Gene Polymorphismrs5186 (A1166C)
Male
Female		SexTotal
A AStudy GroupControlCount154108262
% within
Study
Group		58.8%41.2%100.0%
T2DMCount10894202
% within
Study
Group		53.5%46.5%100.0%
T2DNCount7672148
% within
Study
Group		51.4%48.6%100.0%
Total
% within Study Group		Count338274612
55.2%44.8%100.0%
A CStudy GroupControlCount261642
% within
Study
Group		61.9%38.1%100.0%
T2DMCount162036
% within
Study
Group		44.4%55.6%100.0%
T2DNCount12618
% within
Study
Group		66.7%33.3%100.0%
Total
% within Study Group		Count544296
56.2%43.8%100.0%
C CStudy GroupT2DMCount448
% within
Study
Group		50.0%50.0%100.0%
T2DNCount202
% within
Study
Group		100.0%.0%100.0%
Total
% within Study Group		Count6410
60.0%40.0%100.0%
SNPGenotypeControlT2DMT2DNH
N=304%N=246%N=168%
rs5186A A26286.1820282.1114888.10
A C4213.823614.631810.71
C C00.0083.2521.19

Table 1: Sex wise distribution of study groups on the basis of AGTR1 Gene Polymorphism.

SNPAllelesStudy groupObsHETPredHETHWpvalMAF
rs5186A:CCON0.1380.1290.43690.069
T2DM0.1460.1890.004*0.106
T2DNH0.1070.1220.28760.065

Table 2: Hardy-Weinberg Equilibrium (HWE) test for rs5186 (A>C) of AGTR1 gene among the study groups.

*:Significant Table 3: Hardy-Weinberg Equilibrium (HWE) test for rs5186 (A>C) of AGTR1 gene among the study groups.

SNP A1 A2 Between Study group F_A F_U CHISQ P OR L95 U95

rs5186 C A

CON vs. T2DM 0.1057 0.0690 4.664 0.0308* 1.593 1.041 2.437

CON vs. T2DNH 0.0654 0.0690 0.0444 0.833 0.944 0.553 1.61

T2DM vs. T2DNH 0.0654 0.1057 3.967 0.0463* 0.592 0.352 0.996

  • *;Significant

Table 3: Fisher exact test for allelic association of SNP rs5186 (A>C) of AGTR1 gene among the study groups.

SNPA1A2Between Study groupGENOTRENDDOMREC
rs5186CACONVs.T2DMAFF8/36/20252/44044/2028/238
UNAFF0/42/26242/56642/2620/304
CHISQNA4.26NANA
pNA0.04*NANA
CONVs.T2DNHAFF2/18/14822/31420/1482/166
UNAFF0/42/26242/56642/2620/304
CHISQNA0.0447NANA
pNA0.8326NANA
T2DMVs.T2DNHAFF2/18/14822/31420/1482/166
UNAFF8/36/20252/44044/2028/238
CHISQNA3.31NANA
pNA0.06NANA

Table 4: Fisher model test for SNP rs5186 of AGTR1 gene among the study groups.

*Significant Table 5: Fisher model test for SNP rs5186 of AGTR1 gene among the study groups.

Quantitative
variables		AGTR1 GENE POLYMORPHISMANOVA
AA (n=612)AC (n=96)CC (n=10)FSig.
Mean ± SDMean ± SDMean ± SD
Age (Years)54.91 ± 7.5753.9 ± 7.09955.8 ± 9.3430.8460.43
Height (cm)160.47 ± 9.45160.24 ± 10.29157.72 ± 10.740.4190.658
Weight (kg)61.43 ± 12.3161.18 ± 10.8472.67 ± 15.754.2450.015*
BMI (kg/m2)23.77 ± 3.8323.85 ± 3.9829.89 ± 8.91011.7870.000*
SBP(mmHg)134.87 ± 24.80134.94 ± 23.15138 ± 25.290.080.923
DBP (mmHg)84.33 ± 11.5386.73 ± 10.9484.00 ± 8.431.8520.158
Glucose (mg/dl)130.23 ± 53.986126.58 ± 36.089131.2 ± 38.1420.2090.811
Cholesterol (mg/dl)176.10 ± 39.95183.37 ± 33.14164.27 ± 24.151.9840.138
Triglyceride (mg/dl)160.89 ± 76.39180.83 ± 84.11200.16 ± 64.213.8570.022*
Creatinine (mg/dl)2.33 ± 2.312.07 ± 2.002.11 ± 1.880.5440.581
Total Protein (g/dl)7.55 ± 0.967.67 ± 1.188.76 ± 0.867.7470.000*
Albumin (g/dl)4.21 ± 0.694.25 ± 0.694.62 ± 0.331.910.149
Globulin (g/dl)3.34 ± 0.813.41 ± 0.814.14 ± 0.945.0430.007*

Table 5: Comparison of mean values of different quantitative variables among the study groups based on genotype of AGTR1 gene pol

*Significant Table 6: Comparison of mean values of different quantitative variables among the study groups based on genotype of AGTR1 gene polymorphism.

POPULATIONAlleles AAlleles C
PRESENT STUDYINDIANBENGALEE0.9190.081
1000GENOMESASIANASN0.930.07
CHB0.9480.052
JPT0.9380.062
CHS0.9050.095
EUROPEANEUR0.7280.272
CEU0.6940.306
TSI0.770.23
FIN0.7690.231
GBR0.680.32
IBS0.6790.321
AFRICANAFR0.9740.026
YRI0.9890.011
ASW0.910.09
AMERICANAMR0.7650.235
MXL0.7420.258
PUR0.7910.209
CLM0.7670.233

Table 6: Allele frequencies of AGTR1 gene variant rs5186 in present study groups and World population (1000 GENOME PROJECT) [45].

Figure 2: It is evident that the minor allele frequency is quite low in African population (YRI) where the ‘C’ allele shows a low frequency of 0.011, which is yielding a very low heterozygosity. The ancestral allele (A) frequency is quite high in all populations except in the European population and the lowest frequency among IBS population (0.679). Although European and American populations show quit higher frequency of minor allele, the two Mongoloid Asian populations CHB and JPT show similar profile, whereas the present study Indian Bengali population shows profile similar to the all Asian (ASN) and CHS populations.
Click to enlarge
Figure 2: It is evident that the minor allele frequency is quite low in African population (YRI) where the ‘C’ allele shows a low frequency of 0.011, which is yielding a very low heterozygosity. The ancestral allele (A) frequency is quite high in all populations except in the European population and the lowest frequency among IBS population (0.679). Although European and American populations show quit higher frequency of minor allele, the two Mongoloid Asian populations CHB and JPT show similar profile, whereas the present study Indian Bengali population shows profile similar to the all Asian (ASN) and CHS populations.

Discussion

Insensitivity to insulin or type2 diabetes is diligently associated to the metabolic syndrome [45, 46], and the RAAS have a pivotal role in the insulin sensitivity [47, 48, 49] as well as in the regulation of blood pressure, maintaining stable equilibrium of sodium ion and extracellular fluid volume [50, 51].

In our preceding work we have found that RAAS polymorphisms are genetically susceptible for hypertension, and renal complication associated with diabetes [13, 32, 33, 41]. Though various studies have found the association of RAAS variants with hypertension [52, 53, 54, 55, 56], atherosclerosis [57], progression of renal disease [35, 53, 58], diabetic nephropathy 29], the relevance of RAAS polymorphism regarding insulin resistance yet has not been fully illuminated. Polymorphisms of different candidate of the RAAS i.e. REN, ACE, AGT, AGTR1 have been explained with controversial results [21, 34, 35, 36, 37, 38, 39, 59, 60] mainly elucidated by the diverse ethnic backgrounds of the study population.

Out of several single nucleotide polymorphisms within the AGTR1 gene, the best evaluated polymorphism is rs5186 (A1166C) where nucleotide Adenine (A) is substituted by Cytosine (C). The A allele devoid of restriction enzyme site (DdeI) therefore produce larger fragment, whereas the C allele carries the enzyme-restriction site at nucleotide position 1166, therefore produce smaller fragment [54]. This rs5186 (A1166C) polymorphism of the AGTR1 gene was reported to be associated with a number of cardiovascular outcomes [61, 62, 63, 64], essential hypertension [20, 65, 66], and has been proposed as a predictor of renal injury in T2DM [21]. The C allele (either in homozygous CC or heterozygous AC) carrying Type 2 diabetes patients showed rapid deterioration of renal function than those with the AA genotype and this was confirmed in a later study which showed that the A1166C polymorphism was associated with the development of renal disease and progression to end-stage renal failure [67, 68, 69]. A previous study reported that the A1166C polymorphism may contribute to nephropathy development, particularly in T2DM patients and the homozygote variant genotypes (CC) for the risk of DN [70]. Although a recent Japanese study reported that the impact of C allele on progression of DN in a small number of Japanese women T2DM patients [34]. However, a study from china reported that AGTR1 is not a contributing factor for DN in T2DM patient in Chinese population [71].

The result of our study have replicate findings of previous studies who have reported synergistic effect between the AGTR1 C1166 allele and poor glycemic control on risk of developing nephropathy in type 2 diabetic patients. The present study also reveals that the AGTR1 A1166C polymorphism has a positive association with T2DM (OR =1.593, p < 0.05). This polymorphism with C allele may contribute to diabetic nephropathy development particularly in T2DM patients and this result is in agreement with previous meta-analysis study [70].

Previously it was considered, the RAAS as an endocrine system resulting in the production of angiotensinogen in the liver, which is split by renin released from the renal juxtaglomerular cells [72]. But over the past three decades several studies revealed that local RAAS independently operate from their systemic counterpart [73]. A local RAAS along with its all the members present in the proximal tubular cells of the kidney. Angiotensin II actively produced from the proximal tubular cell, which also secretes angiotensinogen into the urine [73]. Intraluminal angiotensinogen perhaps converted to Ang II in the distal tubules, which leads to the stimulation of sodium channels independent of aldosterone [74]. Poor glycemic control and abnormal quantities of protein in urine could stimulate the synthesis of local Ang II mainly by oxygen species as signal transducers [17]. AGTR1 expression is induced by various stimuli, but down regulated by high conc. of Ang II [17], a feedback mechanism of gene regulation. Now the polymorphic AGTR1 may be insensitive to this down regulation by Ang II and therefore predisposed to renal dysfunction in hyperglycemic condition. It is beyond our scope to investigate this idea, but one can design an experimental set up to explore any such contribution of AGTR1 gene polymorphism to the renal dysfunction in individual who is suffering from poor glycemic control.

Conclusion

To expose a particular disease and also to identify its tendency within a particular population in a particular ethnic background, the delineation of the responsible functional genes of the genome is of great importance which eventually be of support to the doctors for recommending personalized medicine.

The study reveals that the AGTR1 A1166C polymorphism has a positive association with T2DM and C allele may contribute to diabetic nephropathy development particularly in T2DM patients of Bengali population of Eastern India. The present study has to be taken under consideration within its limitations, that it was limited to a specific ethnic group (Eastern Indian Bengali population). The CC genotype individual are relatively shorter and shows higher mean values of weight, BMI, triglyceride, total protein, globulin compared to AA and AC genotype groups. A larger study from different ethnic groups will be needed to confirm for any contribution of AGTR1 gene polymorphism to T2DM complications for development of renal problem or nephropathy. It is to mention here that this research work only deals with the association study (irrespective of gender) between diabetic nephropathy and the genetic variation of AGTR1 gene within its 5’ end of the 3’-untranslated region.

Acknowledgement

We would like to thank the members of the study populations, patients and control participants for voluntarily taking part in this research work and donating their blood samples and cooperation during data collection. We wish to express our deep gratitude to the Director, Anthropological Survey of India, for his kind permission to initiate the work and also for providing financial support.

Funding

This study was funded by the Anthropological Survey of India (Fellowship to Dr. Pulakes Purkait as Junior Research Fellowship and Senior Research Fellowship).

Availability of Data Materials: Although the study is not a clinical trial, it is a genetic study. All data submitted to the Anthropological survey of India.

Conflicts of Interest

The authors declare that they have no competing interests.

Authors’ Contributions

PP was involved in the experiments, screening for gene mutations, performed the statistical analysis as well as participating in the write up of the manuscript; KH contributed to preparation of the manuscript. All authors read and approved the final manuscript.

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@article{halder2020,
  title   = {Association of Angiotensin II Type I Receptor (AGTR1) Gene Polymorphism and Type 2 Diabetes & Nephropathy among the Eastern Indian Bengali Patients},
  author  = {Halder K and Purkait P},
  journal = {Diabetes & Obesity International Journal},
  year    = {2020},
  volume  = {5},
  number  = {2},
  doi     = {10.23880/doij-16000224}
}
Halder K and Purkait P (2020). Association of Angiotensin II Type I Receptor (AGTR1) Gene Polymorphism and Type 2 Diabetes & Nephropathy among the Eastern Indian Bengali Patients. Diabetes & Obesity International Journal, 5(2). https://doi.org/10.23880/doij-16000224
TY  - JOUR
TI  - Association of Angiotensin II Type I Receptor (AGTR1) Gene Polymorphism and Type 2 Diabetes & Nephropathy among the Eastern Indian Bengali Patients
AU  - Halder K and Purkait P
JO  - Diabetes & Obesity International Journal
PY  - 2020
VL  - 5
IS  - 2
DO  - 10.23880/doij-16000224
ER  -