Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus

Abstract

Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC + CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p < 0.0001, OR = 4.9, 95% CI = 2.7-8.8; p ˂ 0.0001, OR = 3.6, 95% CI = 2.2-5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC + CC) genotypes and C-allele compared with controls (p ˂ 0.0001, OR = 5.1, 95% CI = 2.7-9.7; p ˂ 0.0001, OR = 3.5, 95% CI = 2.1-6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p ˂ 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.

Association of a common genetic variant (insertion/deletion) in ACE gene with prostate cancer susceptibility in a Tunisian population

“… 11 , 12 , 13 , 14 , 15 , 16 RAS includes Angiotensin‐Converting Enzyme ( ACE ), the key effector peptide of RAS, converts angiotensin‐I to angiotensin‐II and splits bradykinin into inactive fragments. 11 The alteration of ACE enzyme activity was associated with the development of many diseases such as COVID, 17 , 18 hypertension, and cardiovascular diseases (CVDs), 19 , 20 renal pathology, 21 Alzheimer disease, 22 , 23 polycystic ovarian syndrome, 24 and cancers. 25…”

The Renin-Angiotensin System: The Challenge behind Autoimmune Dermatological Diseases

“…The AT1R gene [92] and AT2R gene [93] polymorphisms might be considered as potential risk factors for children from Egypt with SLE [92,93]. Shoaib et al [92] hypothesized that the AT1R gene polymorphism observed in SLE patients reduces the regulatory effect of miRNA155 on AT1R gene expression, leading to high levels of AT1R. This, in turn, contributes to enhanced pro-inflammatory effects.…”

“…This, in turn, contributes to enhanced pro-inflammatory effects. In addition, elevated serum ACE levels in SLE patients stimulate the production of Ang II, which acts through the AT1Rs and intensifies the pro-inflammatory effects, increasing the susceptibility to SLE [92].…”

Tumor necrosis factor receptor II and PTPN22 genes polymorphisms and the risk of systemic lupus erythematosus in Egyptian children

“…3 Regarding Egyptian children with SLE, many susceptibility genes were previously studied as Interleukin-17F rs763780 and rs2397084 5 and Angiotensin II type 1 receptor genes polymorphism. 6 In the present study, we focused on genes controlling two important cytokines in pathogenesis of SLE as Tumor necrosis factor-oe (TNF-oe) and interferon oe (INF-oe). Both cytokines were found to cross regulate each other.…”

“…3 Regarding Egyptian children with SLE, many susceptibility genes were previously studied as Interleukin-17F rs763780 and rs2397084 5 and Angiotensin II type 1 receptor genes polymorphism. 6…”