The association of <i>ACE</i> gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan

Wang, Yuying; Peng, Wen; Zhang, Xiaoxue; Qiao, Huibo; Wang, Li; Zhang, Xu; Wu, Chenguang

doi:10.1177/1470320316666749

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…Thus, COVID-19-associated decrease in ACE2 most likely results in disruption of the ACE/ACE2 balance in the kidney leading to sustained activation of ACE and Ang-II activities and kidney damage. ACE insertion/deletion polymorphism is also associated with diabetic kidney disease, the frequency of DD and ID genotype distribution being higher compared with non-diabetic kidney disease cohorts, leading to functional decline [50,51]. The above observations suggest that presence of the DD genotype of ACE in patients with COVID-19 infection may be associated with severe respiratory distress compared with the other genotypes.…”

Section: Ace Insertion/deletion (Id) Polymorphisms: Prevalencementioning

confidence: 89%

Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

Sarangarajan¹,

Winn

Kiebish³

et al. 2020

J. Racial and Ethnic Health Disparities

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Rationale Hypertension, obesity and diabetes are major risk factors associated with morbidities underlying COVID-19 infections. Regression analysis correlated presence of ACE insertion/deletion (I/D) polymorphism to COVID-19 incidence and mortality. Furthermore, COVID-19 prevalence correlated to allele frequency of angiotensin-converting enzyme (ACE) deletion (D) polymorphism within the European population. Objective Homozygous ACE deletion polymorphism is associated with increase in ACE and angiotensin II (Ang-II), sustained levels can result in inflammation, fibrosis and organ damage. The ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for COVID-19 infection and outcomes. The study objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities providing rationale for therapeutic utility of ACE-I/ARBs to improve outcomes. Method and Results The Allele Frequency Database (ALFRED) was queried for frequency of rs4646994 representing ACE I/D polymorphism. In a total of 349 worldwide population samples, frequency of ACE D allele was higher in European, Asian, and Africans cohorts. In the USA, the frequency of ACE D allele was higher in non-Hispanic Black compared with non-Hispanic White and Mexican Americans. Conclusion COVID-19 binding mediated reduction/inactivation of ACE-II can increase ACE/Ang-II signalling pathway and related pathologies. The presence of ACE DD polymorphism with COVID-19 infection likely augments ACE/Ang-II activities, increasing severity of COVID-19 morbidities and impacts outcomes. Thus, ethnic prevalence of ACE DD polymorphism can explain in part the severity of COVID-19 morbidity providing rationale for the use of ACE-I/ARBs to improve outcomes.

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Section: Ace Insertion/deletion (Id) Polymorphisms: Prevalencementioning

confidence: 89%

Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

Sarangarajan¹,

Winn

Kiebish³

et al. 2020

J. Racial and Ethnic Health Disparities

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“…It has certain protective effects on glomeruli by inhibiting angiotensin. Evidences from previous studies suggested that valsartan could remarkably lower the glomerular filtration rate and the production of proteinuria, playing a protective role in renal function in patients with type 2 diabetes [ 33 , 34 ]. α-lipoic acid is an antioxidant that can protect β cells, lower the level of cholesterol, reduce proteinuria and mesangial expansion in diabetic mice, thus inhibiting the development and progression of DN [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of valsartan combined with α-lipoic acid on renal function in patients with diabetic nephropathy: a systematic review and meta-analysis

Sun

Jiang

Cai³

2021

BMC Endocr Disord

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Background Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes, valsartan and α-lipoic acid alone or in combination has been used for the treatment of patients with DN. However, some results in these clinical reports were still controversial. The purpose of this study was to evaluate the efficacy of valsartan combined with α-lipoic acid on renal function in patients with DN. Methods We searched the electronic databases including PubMed, Sciencedirect, EMBASE, Cochrane library, Chinese national knowledge infrastructure (CNKI) and Wanfang databases, and the publication deadline was limited to January 2020. Randomized controlled trials (RCTs) evaluating the effects of valsartan combined with α-lipoic acid in DN patients were included. Pooled estimates were conducted using a fixed or random effect model. The outcomes included urinary albumin excretion rate (UAER), and the level of urinary albumin, β2-microglobulin (β2-MG), hypersensitive C-reactive protein (hs-CRP) and oxidative stress. Results 11 studies with 1294 participants were included in this study. The pooled analysis indicated that α-lipoic acid combined with valsartan could remarkably reduce UAER (P < 0.00001, SMD = -1.95, 95%CI = -2.55 to − 1.20; P = 0.03, SMD = -0.85, 95%CI = -1.59 to − 0.1) and the level of urinary albumin (P = 0.001, SMD = -1.48, 95%CI = − 2.38 to − 0.58; P = 0.01, SMD = -1.67, 95%CI = -3.00 to − 0.33), β2-MG (P < 0.001,SMD = − 2.59, 95%CI = -3.78 to − 1.40; P = 0.03, SMD = -0.48, 95%CI = -0.93 to − 0.04) when compared with valsartan or lipoic acid monotherapy in patients with DN. However, there was no significant difference in the level of hs-CRP among the three therapies (P = 0.06, SMD = -2.80, 95%CI = -5.67 to 0.07; P = 0.10, SMD = -0.42, 95%CI = − 0.92 to 0.08). In addition, α-lipoic acid combined with valsartan markedly increased the level of SOD (P = 0.03, SMD = 1.24, 95%CI = 0.32 to 1.03; P = 0.0002, SMD = 0.68, 95%CI = 0.32 to 1.03) and T-AOC (P < 0.00001, SMD = 0.89, 95%CI = 0.62 to 1.16; P = 0.02, SMD = 0.58, 95%CI = 0.10 to1.07), and reduced the level of MDA(P = 0.0002, SMD = -1.99, 95%CI = -3.02 to − 0.96; P = 0.0001, SMD = -0.69, 95%CI = -1.04 to − 0.34). Conclusions α-lipoic acid combined with valsartan could significantly reduce the level of urinary albumin and oxidative stress, increase antioxidant capacity and alleviate renal function damage in patients with DN, and this will provide a reference for the selection of treatment drugs for DN.

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“…It also exists in glomerular endothelial cells, mesangial cells, podocytes, and distal nephrons. Due to the crucial role of ACE in the RAAS, a large number of studies have linked its polymorphisms to the development of diabetic microvascular complications, such as DN [63]. ACE I/D is the most susceptible locus for DN.…”

Section: Genes Related To the Renin-angiotensin-aldosterone Systemmentioning

confidence: 99%

The Susceptibility Genes in Diabetic Nephropathy

Wei

Xiao

et al. 2018

Kidney Dis

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Background: Diabetes mellitus (DM) poses a severe threat to global public health. Diabetic nephropathy (DN) is one of the most common complications of diabetes and the leading cause of end-stage renal disease (ESRD). Approximately 30–40% of DM patients in the world progress to ESRD, which emphasizes the effect of genetic factors on DN. Family clustering also supports the important role of hereditary factors in DN and ESRD. Therefore, a large number of genetic studies have been carried out to identify susceptibility genes in different diabetic cohorts. Extensive susceptibility genes of DN and ESRD have not been identified until recently. Summary and Key Messages: Some of these associated genes function as pivotal regulators in the pathogenesis of DN, such as those related to glycometabolism and lipid metabolism. However, the functions of most of these genes remain unclear. In this article, we review several susceptibility genes according to their genetic functions to make it easier to determine their exact effect on DN and to provide a better understanding of the advancements from genetic studies. However, several challenges associated with investigating the genetic factors of DN still exist. For instance, it is difficult to determine whether these variants affect the expression of the protein they encode or other cytokines. More efforts should be made to determine how these genes influence the progression of DN. In addition, many results could not be replicated among races, suggesting that the association between genetic polymorphisms and DN is race-specific. Therefore, large, well-designed studies involving more relevant variables and ethnic groups and more relevant functional studies are urgently needed. These studies may be beneficial and retard the progression of DN by early intervention, especially for patients who carry certain risk alleles or genotypes.

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The association of ACE gene polymorphism with diabetic kidney disease and renoprotective efficacy of valsartan

Cited by 12 publications

References 26 publications

Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

Effects of valsartan combined with α-lipoic acid on renal function in patients with diabetic nephropathy: a systematic review and meta-analysis

The Susceptibility Genes in Diabetic Nephropathy

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