Association between genetic polymorphism of the angiotensin-converting enzyme and diabetic nephropathy: a meta-analysis comprising 26,580 subjects

Wang, Furu; Fang, Qun; Yu, Nian; Zhao, Dan; Zhang, Yimei; Wang, Jin; Wang, Quan; Zhou, Xin‐Da; Cao, Xiaofeng; Fan, Xiangyong

doi:10.1177/1470320311417655

Cited by 62 publications

(53 citation statements)

References 89 publications

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“…Our observations relating to the relationship of ACE polymorphism with diabetic nephropathy were in agreement with other previous studies, a meta-analysis study verified that II genotype has compact the risk of diabetic nephropathy [16]. Our results were also supported by another meta-analysis data, where reported considerable involvement between the ACE DD polymorphism and the possibility of DN [17]. In the same line, several studies in different population have reported that a strong relationship between the ACE DD genotype and the risk for diabetic nephropathy was reported in Malaysian [18], British Caucasian [19], Bahraini [20], Japanese [21], Korean [22], and Americans [14] populations.…”

Section: Discussionsupporting

confidence: 82%

The Combined Effect of ACE, TCF7L2, and PPARGC1A Gene Polymorphisms in Diabetic Nephropathy

et al. 2017

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Keywords: Diabetic nephropathy (DN), Type 2 diabetes mellitus (T2DM), Angiotensinconverting enzyme (ACE), Transcription factor 7-like 2 (TCF7L2), Peroxisome proliferator activated receptor gamma coactivator-1 alpha (PPARGC1A). 62T HIS study was performed for investigation the relationship between variants of ACE, TCF7L2 and PPARGC1A gene polymorphisms individually or in combination with the development of nephropathy in T2DM.T he study was included 85 T2DM patients (45 with nephropathy and 40 without nephropathy), and 45 healthy control subjects. The I/D polymorphism of ACE gene was evaluated by PCR method. The polymorphisms rs7903146 (C/T) of TCF7L2 gene and Gly482Ser (G/A) and Thr394Thr (G/A) of PPARGC1A gene were evaluated by PCR-RFLP analysis.The frequency of ACE DD genotype and D allele was significantly higher in DN patients when compared to diabetic without nephropathy. The frequency of TCF7L2 rs7903146 TT genotype and T allele were significantly associated with DN patients compared to T2DM. Moreover, a significant association in A allelic frequencies was observed in DN cases compared to T2DM patients without nephropathy. No differences in the genotypic and allelic frequencies between T2DM patients with and without nephropathy were found for the Thr394Thr polymorphism.Our study suggested that candidate gene polymorphisms I/D of ACE, rs7903146 of TCF7L2 and Gly482Ser of PPARGC1A individually or in combination may act as susceptibility biomarkers for nephropathy in T2DM. IntroductionThe pathogenesis of diabetic nephropathy (DN) has many genetic and environmental factors contributing to its developing and progression. The ACE gene polymorphism is insertion/deletion (I/D) of a 287-bp sequence of DNA in the intron 16 that could be relating to circulating ACE level which involved in the etiology of DN [1,2].The transcription factor 7-like 2 (TCF7L2) is located on chromosome 10q25.3 which considered the main susceptibility gene for T2DM [3]. Wu [4] was reported that the TCF7L2 gene may be contributed to the etiology of DN in combination with other genes. However, Hussain [5] showed an association between TCF7L2 gene and DN, but this association is not independent of T2DM.Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) gene is located on chromosome 4p15.1 that is a biological and positional candidate for T2DM progression [6]. Furthermore, PPARGC1A Gly482Ser polymorphism is associated with diabetic nephropathy [7].There was no enough research available for the genetic combination of ACE, TCF7L2 and PPARGC1A gene polymorphisms in DN. Therefore the aim of this study was to assess the genetic interaction between ACE, TCF7L2 and PPARGC1A polymorphisms in DN development. Subjects and Methods Study subjectsThis study recruited 85 T2DM patients diagnosed at least 5 years before, the patients consecutively attended the diabetes clinic of Internal Medicine Department; Kasr El-Aini Hospital affiliated to Cairo University. Forty five of them (12 males and 33 females) with nephropathy, while ...

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Section: Discussionsupporting

confidence: 82%

The Combined Effect of ACE, TCF7L2, and PPARGC1A Gene Polymorphisms in Diabetic Nephropathy

et al. 2017

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“…Therefore, we suggest that the genetic variation at the ACE locus as D/D variant in intron 16, contribute to an increased risk of nephropathy in T2DM patients, but not extent of DN severity (as the allelic or genotypic distribution was comparable between the two DN groups) in studied population. Our findings were in conformity with other studies [26][27][28][29][30][31] but not all [32,55,56]. This difference may possibly be due to different races, methods of quantitation and patient selection; as proteinuria in adults is a multifactorial condition frequently linked with diabetes, the issue of whether proteinuria is due to diabetes or some other etiology remains debatable, but there was no uncertainty in our group of patients on the role of T2DM in diabetic nephropathy constitution as we excluded the patients who had proteinuria/renal disorders before their diabetes was diagnosed, thus we confined our study to diabetic kidney diseases.…”

Section: Discussionsupporting

confidence: 81%

“…Thus, the contribution of ACE gene polymorphism to the heritable part of risk for diabetic nephropathy seems important, and is supported by findings from published meta-analyses [28,62] along with other studies done among Indians [31,63], Japanese [29], French [64], Egyptian [65] and Taiwan [27] diabetic patients. However, our results do not coincide with studies done among Chinese [66], Tunisian [55], French [56], Turkish [34] and Iranian [67] diabetic cases.…”

Section: Discussionsupporting

confidence: 54%

“…This polymorphism was associated with circulating ACE levels [23][24][25] and owing to its central role in the regulation of blood pressure, sodium metabolism and renal hemodynamics [16,17], it is reasonable to hypothesize that genetic variation of ACE I/D contributes to the development of DN and numerous studies have addressed the role of this polymorphism in the complex etiology of DN, albeit with conflicting results i.e. several studies have demonstrated [26][27][28][29][30][31] or refuted [32][33][34] the role of ACE D variant as candidates for the development of DN. The discrepant finding among studies is attributed to genetic and environmental heterogeneity among different populations.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

et al. 2013

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Genetic polymorphism as described with angiotensin-converting enzyme gene has been proposed as a putative mediator of diabetic nephropathy. We substantiate the hypothesis that genetic variants of the ACE have significant impacts on diabetic nephropathy. To assess the possible association between the three ACE polymorphic variants and DN in an ethnically homogeneous type 2 diabetic population from Kutch region. A 287-bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction using a case-control approach conducted with 309 unrelated type 2 diabetic patients of Kutch origin (159 Ahir and 150 Rabari, with [10 years duration of T2DM). Of the patients, 143 had nephropathy {AER[30 mg/day (Ahir, n:73 and Rabari, n:70)} and were considered as cases; all others {n:166 (86 Ahir and 80 Rabari)} were normoalbuminuric (AER\30 mg/day) and were treated as controls. Suitable descriptive statistics was used for different variables. Genotype frequencies in all groups were all in accordance with the Hardy-Weinberg equilibrium. Genotypic distribution was significantly different between cases and controls (Ahir: x 2 :8.87, 2 d.f. p = 0.0118; Rabari: x 2 :11.01, 2 d.f. p = 0.0041). Multivariate logistic regression analysis revealed that DD genotype was a significant and strongest independent predictor of microalbuminuria (Ahir: p = 0.0362, OR = 2.65, 95 % CI 1.89-6.36; Rabari: p = 0.024, OR = 2.81, 95 % CI 1.9-6.65). However, it did not independently change the odds of having macroalbuminuria versus microalbuminuria. Analysis of the association under various genetic models revealed that ACE I/D polymorphic variant contribute to DN susceptibility under recessive mode only. Genetic variation at the ACE locus as D/D variant in intron 16, contribute to an increased risk of nephropathy in T2DM patients but not extent of DN severity, and thus this polymorphism might be considered as genetic risk factors for DN among patients with type 2 diabetes.

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“…Wang et al performed a meta-analysis of 14,108 DKD cases and 12,472 controls from 63 published studies [75]. When the authors included all ethnicities and both diabetes types, there was a significant association between an ACE insertion/deletion polymorphism and the risk of DKD.…”

Section: Candidate Gene Association Studiesmentioning

confidence: 99%

Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy

Davoudi¹,

Sobrin²

2015

Rev Diabet Stud

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■ AbstractBoth type 1 and type 2 diabetes mellitus can lead to the common microvascular complications of diabetic retinopathy, kidney disease, and neuropathy. Diabetic patients do not universally develop these complications. Long duration of diabetes and poor glycemic control explain a lot of the variability in the development of microvascular complications, but not all. Genetic factors account for some of the remaining variability because of the heritability and familial clustering of these complications. There have been a large number of investigations, including linkage studies, candidate gene studies, and genome-wide association studies, all of which have sought to identify the specific variants that increase susceptibility. For retinopathy, several genomewide association studies have been performed in small or midsize samples, but no reproducible loci across the studies have been identified. For diabetic kidney disease, genomewide association studies in larger samples have been performed, and loci for this complication are beginning to emerge. However, validation of the existing discoveries, and further novel discoveries in larger samples is ongoing. The amount of genetic research into diabetic neuropathy has been very limited, and much is dedicated to the understanding of genetic risk factors only. Collaborations that pool samples and aim to detect phenotype classifications more precisely are promising avenues for a better explanation of the genetics of diabetic microvascular complications.

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Association between genetic polymorphism of the angiotensin-converting enzyme and diabetic nephropathy: a meta-analysis comprising 26,580 subjects

Abstract: Our study suggested that the ACE I/D polymorphism may contribute to DN development, especially in the Asian group with T2DM.

Cited by 62 publications

References 89 publications

The Combined Effect of ACE, TCF7L2, and PPARGC1A Gene Polymorphisms in Diabetic Nephropathy

The Combined Effect of ACE, TCF7L2, and PPARGC1A Gene Polymorphisms in Diabetic Nephropathy

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy

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