Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

Ng, Daniel P.K.; Tai, Bee Choo; Koh, David; Tan, Ken Wei; Chia, Kee Seng

doi:10.1007/s00125-005-1726-2

Cited by 133 publications

(104 citation statements)

References 68 publications

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“…This result raises the thought that the D polymorphism is associated with the development of nephropathy in T2DM patients. 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].…”

Section: Discussionsupporting

confidence: 93%

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: 93%

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

et al. 2017

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“…Genetically, deletion in intron 16 of the human ACE gene results in an increased ACE activity in both plasma and tissue level (Danser et al 1995;Mizuiri et al 2001;Rigat (Ng et al 2005;Staessen et al 1997). Whereas meta-analyses confirm a role for the D allele as a renal and cardiovascular risk factor (Samani et al 1996), the significance of genetically high/low ACE is still controversial (Staessen et al 1997).…”

Section: Discussionmentioning

confidence: 99%

Differential ACE expression among tissues in allele-specific Wistar rat lines

et al. 2009

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In humans, the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene accounts for half of the variance in plasma ACE activity. The deletion allele is associated with high plasma ACE activity, cardiovascular disease, and renal disease. In rat, a similar association is found between the B and L alleles of a microsatellite marker in the ACE gene. We identified the B/L variation in the Wistar outbred rat and bred two lines homozygous for the two alleles (WU-B and WU-L). ACE activity was measured in serum, heart, kidney, and aorta homogenates. Immunohistochemistry and ACE mRNA expression were performed in heart, kidney, and aortic tissue. Aortic rings were collected and stimulated with AngI, AngII, and AngI with Lisinopril to measure ACE functional activity by vasoconstrictor response. Serum, heart, and kidney ACE activity and kidney mRNA expression were two-fold higher in WU-B. Kidney staining showed a clear difference in tubular ACE expression, with more staining in WU-B. While in aorta ACE activity and mRNA expression was twofold higher in WU-L, functional conversion of AngI was higher in WU-B, indicating either a functional difference in AngI to AngII conversion between the two alleles due to different splicing or the presence of other factors involved in the conversion that are differentially expressed as the result of differences in the ACE alleles. The newly developed WU-B and WU-L lines show tissue-specific differences in ACE expression and activity. This provides an experimental tool to study the pathophysiologic consequences of differences in ACE alleles in renal and cardiovascular disease.

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“…The role of ACE I/D polymorphism in the pathogenesis of DN has been investigated in various ethnic groups with inconsistent results (6,11,17,18). Ethnicity is one of the most important factors, which determines the role of ACE gene polymorphism in the susceptibility to DN.…”

Section: Ace I/d Polymorphism: Onset and Progression Of Diabetic Nephmentioning

confidence: 99%

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Rahimi¹

2012

J Nephropathol

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Implication for health policy/practice/research/medical education:The presence of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with highest systemic and renal ACE levels, compared with the lowest ACE activity in carriers of II genotype. Most studies confirmed that ACE I/D polymorphism is involved in the susceptibility to overt nephropathy with protective role of ACE II genotype against the disease in both type 1 and 2 diabetes mellitus. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Results:The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. Conclusions: In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.Review Article

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Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

Cited by 133 publications

References 68 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

Differential ACE expression among tissues in allele-specific Wistar rat lines

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

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