Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis

Abstract

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( P<0.0001; odds ratio (OR) 2.4; 95% confidence interval (CI) 1.7-3.3) and the D allele was more frequent than the I allele in systemic lupus erythematosus patients in comparison to controls ( P < 0.0001; OR = 2.2; 95% CI = (1.6-3.1). In the lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P < 0.001; OR = 1.98; 95% CI = 1.3-2.9). Conclusion The D allele and DD genotype of the ACE gene appear to be a risk factor for the susceptibility of systemic lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

Angiotensin II type 2 receptor gene polymorphisms and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus

“…1 Lupus nephritis (LN) is a common manifestation of SLE and remains a prevalent cause of morbidity and mortality in SLE. 2…”

“…Ang II is also involved in oxidative-induced damage to blood vessel walls, which leads to vascular diseases. 2…”

“…ACE, interleukin-17A, interleukin-17F, and interferon regulatory factor 5 gene polymorphisms have been reported to be significantly increased in Egyptian children with SLE. 2,3,23…”

“…1 Lupus nephritis (LN) is a common manifestation of SLE and remains a prevalent cause of morbidity and mortality in SLE. 2 The onset of SLE in children represents about 10%-20% of all SLE patients. SLE that initiates in childhood is more severe in onset with higher degrees of organ disturbance, more ferocious clinical course and more-rapid damage than SLE in adults.…”

“…Ang II is also involved in oxidative-induced damage to blood vessel walls, which leads to vascular diseases. 2 In the kidneys, Ang II induces mononuclear cells, stimulates the proliferation of mesangial cells and interstitial fibroblasts, and it increases the synthesis of the extracellular protein matrix resulting in tissue fibrosis. 6 Ang II binds and activates two major types of serpentine, G-protein-coupled receptors that are seven-transmembrane-domain receptors, namely AT1R and AT2R; these two receptors feature minimal similarities.…”