Research Article <i>ACE</i> insertion/deletion polymorphism and diabetic nephropathy: an evidence-based meta-analysis

Abstract

The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism could influence predisposition for diabetic nephropathy (DN) by vascular modulation in the kidney, through a direct effect on cellular hypertrophy. However, studies on the association between this polymorphism and DN report conflicting results. To help determine if this association exists, we conducted a meta-analysis. Published studies until 2018 were researched from electronic databases PubMed/NCBI and Cochrane Library. Thirty studies including 4,774 DN cases and 4,357 individuals without DN were included in this meta-analysis. Extraction of data from all eligible publications was performed by two investigators independently, according to the inclusion and exclusion criteria. We used the statistical software "R" by the overall odds ratio (OR) with a 95% confidence interval to evaluate the association of ACE I/D polymorphism with a possible risk towards DN development. We included various genetic model analyses, sensitivity analyses, and assessments of bias in our meta-L.C. Silveira et al. 2analysis. We found a significant association for ACE I/D polymorphism; the D allele is a predisposing factor for DN in diabetic patients. The risk for development of diabetes complications, such as DN, is highly complex and could be considered multifactorial. In summary, our meta-analysis shows that the ACE I/D polymorphism is associated with susceptibility to DN.

Diagnostic efficacy of cystatin-c in association with different ACE genes predicting renal insufficiency in T2DM

“…Regarding ACE I/D polymorphism, the current study recorded that DD polymorphism was associated with increase in serum creatinine and cyst-c in diabetic patient group. According to Silveira et al 18 , DD polymorphism was associated with DN and T2DM progression. This may be attributed to the functional role of DD polymorphism in the implication of pathological mechanisms through change of endothelial β cells, oxidative stress and renal microvascular complications.…”

“…It is characterized by the presence of a 287 bp Alu repeat sequence (insertion) or absence (deletion) in intron 16 . This produces three genotypes (wild I/I homozygous, heterozygous I/D heterozygote, and mutant homozygous D/D) 17 , 18 . It was recorded in individuals with DD genotype, higher concentration of ACE in both tissue and plasma ACE in comparison with either ID of II genotypes 19 , 20 .…”

“…Silveira et al 18 revealed that ACE insertion (I)/deletion (D) polymorphism could cause instability of RAS as well as dysregulation of micro and macrocirculation and electrolytic homeostasis of the kidney. Moreover, it could affect or lead to DN through a direct effect on cellular hypertrophy resulting vascular modulation in the kidney.…”

No Association of Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) Gene Polymorphism in the Susceptibility to Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients: An Updated Meta-Analysis

“…The main components of this system are renin, angiotensinogen (AGT), Angiotensin I and II (Ang I and Ang II), Angiotensin-converting enzymes 1 and 2 (ACE and ACE2), and type 1 (AT1R) and type 2 receptors (AT2R). ACE hyperactivation increases the synthesis of the vasoconstrictor molecule Ang II [ 36 ]. Ang II alters glucose homeostasis by inhibiting insulin signal transduction, reducing glucose uptake, increasing insulin resistance, and destroying pancreatic β cells by inducing oxidative stress [ 37 ].…”