Association of angiotensin-converting enzyme (ACE) I/D variation with biochemical parameters and oxidative stress markers in systemic lupus erythematosus patients in west of Iran

• Published in: Molecular biology reports Vol. 50; no. 10; pp. 8201 - 8212
• Main Authors: Kiani, Amir, Elieh-Ali-Komi, Daniel, Bahrehmand, Fariborz, Mostafaei, Shayan, Vaisi-Raygani, Asad, Baniamerian, Hosein, Aghaz, Farank, Tanhapour, Maryam, Shakiba, Ebrahim, Rahimi, Zohreh, Pourmotabbed, Tayebeh
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2023; Springer Nature B.V
• Subjects: ACE protein; Alleles; Angiotensin; Angiotensin II; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Enzymes; Gene deletion; Gene frequency; Genotype & phenotype; Genotypes; Histology; Life Sciences; Lupus; Medicin och hälsovetenskap; Morphology; Neopterin; Original Article; Oxidative stress; Paraoxonase; Peptidyl-dipeptidase A; Risk assessment; Serum levels; Single-nucleotide polymorphism; Systemic lupus erythematosus; Variation; Iran; gene insertion/deletion (I/D) variation; Systemic lupus erythematosus; rs1799752; rs4340; Angiotensin-converting enzyme; rs4646994; rs13447447; ACE gene insertion/deletion (I/D) variation
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-023-08685-x

Purpose We aimed to study insertion/deletion (I/D) variation (rs4646994) of ACE gene in a group of SLE patients in west of Iran and its possible relationship with oxidative stress. Method and results Genotypes and allele frequencies related to ACE (I/D) variation were determined in 108 SLE patients and 110 gender and age-matched healthy controls using PCR. Neopterin, malondialdehyde (MDA), and serum lipid concentrations were determined by HPLC and enzyme assay respectively. The overall distribution of ACE I/D genotypes in SLE patients was different from that of the control group (P = 0.005). DD genotype compared to ID genotype increased the risk of SLE (OR = 2.57, 95% CI 1.4–4.8, P = 0.003). ID genotype compared to the II genotype decreased the risk of disease (OR = 0.45, 95% CI 0.2–0.99, p = 0.042). SLE patients with DD, ID, and II genotypes had lower paraoxonase (PON) activity and higher serum levels of MDA and neopterin versus control patients. We also detected a significant protective effect against SLE in presence of ACE I alleles and lack of angiotensin II receptor, type 1 ( AGTR1 ) A1166C (NCBI reference SNP id: rs5186), C alleles in this study (OR = 0.31, 95% CI 0.14–0.68, P = 0.002). Conclusions Carriers of the DD genotype of ACE gene with higher serum concentrations of neopterin and MDA, and lower PON activity had a high risk to develop SLE, while ID genotype decreased the risk of disease development by 2.22 times compared to II genotype.