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SM Journal of Nephrology and Kidney Diseases

Is There An Association Between Angiotensin II Type 1 Receptor A1166C Gene Polymorphism and Renal Scarring Susceptibility?

[ ISSN : 2576-5450 ]

Abstract Citation Introduction Materials and Methods Data Extraction and Synthesis Statistical Analysis Results Discussion References
Details

Received: 18-Jul-2017

Accepted: 17-Aug-2017

Published: 21-Aug-2017

Tianbiao Zhou*#, Weiji Xie#, Zhijun Lin# and Zhensheng Yang

Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, China
#authors contributed equally

Corresponding Author:

Tianbiao Zhou, Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China, Tel: +86-771-2326191; E-mail: zhoutb@aliyun.com

Keywords

Renal scarring; AT1R: Angiotensin II Type 1 Receptor; A1166C; Gene polymorphism; Meta-analysis

Abstract

Relationship between Angiotensin II Type 1 Receptor (AT1R) A1166C gene polymorphism and renal scarring risk is still controversial. This meta-analysis was performed to evaluate the association of AT1R A1166C gene polymorphism and renal scarring risk susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases of PubMed, Embase and Cochrane Library. Three literatures were identified and included for the analysis of the relationship between AT1R A1166C gene polymorphism and renal scarring risk. We found that AT1R A1166C gene polymorphism was not associated with renal scarring susceptibility using the comparison of patients with scarring vs patients without scarring (C: OR=1.33, 95%CI: 0.83-2.13, P=0.23; CC: OR=1.71, 95%CI: 0.22-13.56, P=0.61; AA: OR=0.69, 95%CI: 0.39-1.21, P=0.20). Furthermore, AT1R A1166C gene polymorphism was also not associated with renal scarring risk using the comparison of patients with scarring vs healthy control. In conclusion, AT1R A1166C gene polymorphism was not associated with renal scarring risk susceptibility. However, more studies should be performed in the future.

Citation

Zhou T, Xie W, Lin Z and Yang Z. Is There An Association Between Angiotensin II Type 1 Receptor A1166C Gene Polymorphism and Renal Scarring Susceptibility? J Nephrol Kidney Dis. 2017; 1(1): 1004. 

Introduction

Renal scarring, a serious complication, often occurs with chronic pyelonephritis in the presence of Vesicoureteral Reflux (VUR) [1]. Urinary Tract Infection (UTI) is the most common factor associated with VUR, and it is a pre-requisite for formation of further renal scarring that may cause later problems, such as hypertension, chronic renal failure and, in most cases, end-stage renal disease. UTI, along with other etiologic factors including VUR, is important in the pathogenesis of scarring [2].

Angiotensin II Type 1 Receptor (AT1R) is the primary pathogenic effector for angiotensin II, and it is a member of the G-protein coupled receptor super family expressed in most tissues, where receptor activation leads to vasoconstriction, water retention and vascular smooth muscle cell proliferation and hypertrophy [3,4]. AT1R signaling is well known for causing tissue damage, such as cardiovascular system, kidneys and retina [5]. AT1R A1166C gene polymorphism, an important mutation of AT1R, might be implicated in the etiology of renal scarring susceptibility and had been investigated in numerous epidemiologic studies. However, the available evidence reported to date is weak, due to sparseness of data or disagreements among studies. There was no meta-analysis to explore the association of AT1R A1166C gene polymorphism with renal scarring risk. We performed this meta-analysis to investigate the relation between AT1R A1166C gene polymorphism and renal scarring susceptibility.

Materials and Methods

Search strategy

The relevant studies were screened from the search engines of PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) on March 1, 2015. The following terms in English were used in PubMed and Cochrane Library to complete the search: “Renal scarring”, “Angiotensin II type 1 receptor”, “AT1R”, “A1166C”. We also extended search spectrum to the “related articles” and the bibliographies of all retrieved studies (Figure 1).

Figure 1: Relationship between AT1R A1166C gene polymorphism and risk of renal scarring (Patients with scarring vs Patients without scarring).

Inclusion criteria

(1) A case–control study; (2) the outcome had to be renal scarring; (3) there had to be at least two comparison groups (renal scarring group vs control group).

Exclusion criteria

(1) Review articles, editorials and case reports (2) Articles did not provide the detail genotype data; (3) Investigating the association of other genes with renal scarring. (4) Investigating the gene expression of AT1R to renal scarring. (5) Multiple publications of the same data from the same study group (Figure 2).

Figure 2: Relationship between AT1R A1166C gene polymorphism and risk of renal scarring (Patients with scarring vs Healthy control).

Data Extraction and Synthesis

The following information was extracted from each study independently by at least 2 investigators: first author’s surname, year of publication, ethnicity of study population, and the number of cases and controls for A1166C genotype. Frequencies of C allele were calculated for case group and control group, from the corresponding genotype distribution. The results were compared and disagreements were resolved by discussion.

Statistical Analysis

Available data was entered into Cochrane Review Manager (RevMan, version 5) and analyzed. The pooled statistic was counted using the fixed effects model, but a random effects model was conducted when the P value of heterogeneity test was less than 0.1 [6,7]. Results were expressed with odds ratios (OR) for dichotomous data, and 95% Confidence Intervals (CI) were also calculated. P<0.05 was required for the overall OR to be deemed statistically significant [8,9]. I2 was used to test the heterogeneity between the included studies.

Results

Study characteristics

According to the inclusion and exclusion criteria, three articles [10 12] were identified for this meta-analysis of the association between AT1R A1166C gene polymorphism and renal scarring susceptibility. All the studies were conducted in Caucasian population. The data of our interest were extracted and shown in Table 1.

Table 1: Characteristics of the studies evaluating the effects of Angiotensin II Type 1 Receptor (AT1R) A1166C gene polymorphism on renal scarring risk.

First author, year Ethnicity   Patients with scarring       Patients without scarring
    CC AC AA Total   CC AC AA Total
Haszon 2002 Caucasian 0 25 18 43   0 12 22 34
Kostić 2004 Caucasian 2 8 6 16   2 10 14 26
Ece 2005 Caucasian 0 10 20 30   0 27 40 67
First author, year Ethnicity   Patients with scarring       Healthy control  
    CC AC AA Total   CC AC AA Total
Haszon 2002 Caucasian 0 25 18 43   2 32 46 80
Kostić 2004 Caucasian 2 8 6 16   15 74 109 198
Ece 2005 Caucasian 0 10 20 30   4 18 34 56

Association of the AT1R A1166C gene polymorphisms with renal scarring risk (patients with scarring vs patients without scarring): In this meta-analysis, no significant association between AT1R A1166C gene polymorphism and renal scarring susceptibility using the comparison of patients with scarring vs patients without scarring (C: OR=1.33, 95% CI: 0.83-2.13, P=0.23; CC: OR=1.71, 95% CI: 0.22 13.56, P=0.61; AA: OR=0.69, 95% CI: 0.39-1.21, P=0.20). (Table 2).

Table 2: Meta analysis of the association of AT1R A1166C gene polymorphism with risk of renal scarring.

Genetic Studies Q test Model OR P
contrasts number P value selected (95%CI)  
Patients with scarring vs Patients without scarring
C vs A 3 0.27 Fixed 1.33(0.83, 2.13) 0.23
CC vs AC+AA 3 - Fixed 1.71(0.22, 13.56) 0.61
AA vs AC+CC 3 0.15 Fixed 0.69(0.39,1.21) 0.2
Patients with scarring vs Healthy control
C vs A 3 0.21 Fixed 1.21(0.81, 1.80) 0.36
CC vs AC+AA 3 0.33 Fixed 0.68(0.20,2.33) 0.54
AA vs AC+CC 3 0.27 Fixed 0.68(0.41, 1.13) 0.14

Association of the AT1R A1166C gene polymorphisms with renal scarring risk (patients with scarring vs healthy control): In this meta-analysis, AT1R A1166C gene polymorphism was also not associated with the susceptibility of renal scarring using the comparison of patients with scarring vs healthy control (C: OR=1.21, 95%CI: 0.81-1.80, P=0.36; CC: OR=0.68, 95%CI: 0.20-2.33, P=0.54; AA: OR=0.68, 95%CI: 0.41-1.13, P=0.14; Table 2).

Discussion

We performed this investigation using meta-analysis method for the association of AT1R A1166C gene polymorphism with renal scarring susceptibility, three studies were recruited. Meta analysis of multiple studies has a role in offering an association with such potentials and the results from meta-analysis might be more convincing compared with those from separate studies. In our meta-analysis, we found the difference of distribution of C allele, CC homozygous and AA genotype between patients with renal scarring group and patients without renal scarring group was not statistically different. Furthermore, we also found that the distribution difference of C allele, CC homozygous and AA genotype between patients with renal scarring group and healthy control group was also not statistically different. It seemed that AT1R A1166C gene polymorphism was not associated with the susceptibility of renal scarring.

In previous, there was no any meta-analysis to explore this relationship. Our meta-analysis reported firstly and included three studies for this meta-analysis. However, the number of included studies in our meta-analysis was small, and better designed studies should be performed in the further.

In our study, we might draw the conclusion that AT1R A1166C gene polymorphism was not associated with the susceptibility of renal scarring. However, these findings should be regarded cautiously because many other ingredients, such as heterogeneity of enrolled cases, limited statistical power, variable study designs and different interventions, were closely related to affect the results.

In conclusion, the results in our study supported that AT1R A1166C gene polymorphism was not associated with the susceptibility of renal scarring. However, more case-control association investigations on larger, stratified populations are required to further clarify the role of AT1R A1166C gene polymorphism in renal scarring susceptibility.

References

1. Ichino M, Kusaka M, Kuroyanagi Y, Mori T, Morooka M, Sasaki H, Shiroki R, et al. Urinary neutrophil-gelatinase associated lipocalin is a potential noninvasive marker for renal scarring in patients with vesicoureteral reflux. J Urol. 2010; 183: 2001-2007.

2. Mir S, Ertan P, Ozkayin N. Risk factors for renal scarring in children with primary vesicoureteral reflux disease. Saudi J Kidney Dis Transpl. 2013; 24: 54-59.

3. Zhou TB, Yin SS, Jiang ZP. Association of angiotensin II type-1 receptor A1166C gene polymorphism with the susceptibility of end-stage renal disease. J Recept Signal Transduct Res. 2013; 33: 325-331.

4. Zhou TB, Jiang ZP, Zhou JF, Zhang YM. Association of angiotensin II type-1 receptor A1166C gene polymorphism with the susceptibility of immunoglobulin A nephropathy. Ren Fail. 2015: 37: 359-362.

5. Yin Y, Huang SW, Zheng YJ, Dong YR. Angiotensin II type 1 receptor blockade suppresses HO-induced retinal degeneration in photoreceptor cells. Cutan Ocul Toxicol. 2014: 34: 307-312.

6. Zhou TB, Yin SS, Liang R: A meta-analysis of the association between angiotensin-converting enzyme insertion/deletion gene polymorphism and end-stage renal disease risk in IgA nephropathy patients. J Renin Angiotensin Aldosterone Syst. 2013; 14: 235-241.

7. Zhou TB, Yin SS, Qin YH. Association of angiotensinogen M235T gene polymorphism with end-stage renal disease risk: a meta-analysis. Molecular Biology Reports. 2013; 40:765-772.

8. Zhou TB, Jiang ZP, Zhou JF, Su N. Relationship between chemokine receptor 5 Delta32/W gene polymorphism and lupus nephritis. Hum Immunol. 2014;75: 968-972.

9. Zhou TB, Zhao HL, Fang SL, Drummen GP. Association of transforming growth factor-beta1 T869C, G915C, and C509T gene polymorphisms with rheumatoid arthritis risk. J Recept Signal Transduct Res 2014; 34: 469-475.

10. Haszon I, Friedman AL, Papp F, Bereczki C, Baji S, Bodrogi T. ACE gene polymorphism and renal scarring in primary vesicoureteric reflux. Pediatr Nephrol. 2002; 17: 1027-1031.

11. Kostic M, Stankovic A, Zivkovic M, Peco-Antic A, Jovanovic O, Alavantic D, et al. ACE and AT1 receptor gene polymorphisms and renal scarring in urinary bladder dysfunction. Pediatr Nephrol. 2004; 19: 853-857.

12. Ece A, Tekes S, Gurkan F, Bilici M, Budak T. Polymorphisms of the angiotensin converting enzyme and angiotensin II type 1 receptor genes and renal scarring in non-uropathic children with recurrent urinary tract infection. Nephrology (Carlton). 2005; 10: 377-381.

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