Association of AIRE (rs2075876), but not CTLA4 (rs231775) polymorphisms with systemic lupus erythematosus

• Published in: Gene Vol. 768; p. 145270
• Main Authors: Alghamdi, Saleh A., Kattan, Shahad W., Toraih, Eman A., Alrowaili, Majed G., Fawzy, Manal S., Elshazli, Rami M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.02.2021
• Subjects: Adult; AIRE (rs2075876); AIRE Protein; alleles; Case-Control Studies; complement; CTLA-4 Antigen - genetics; CTLA4 (rs231775); DNA; Egypt; Female; Gene Frequency - genetics; Genetic Association Studies; Genetic polymorphisms; Genetic Predisposition to Disease - genetics; Genome - genetics; Genotype; genotyping; Humans; infection; lupus erythematosus; Lupus Erythematosus, Systemic - genetics; Male; patients; Polymorphism, Single Nucleotide - genetics; risk; SLE; T-lymphocytes; Transcription Factors - genetics; Egypt; SLEDAI; CTLA4 (rs231775); AIRE; CTLA4; AIRE (rs2075876); SLE; Genetic polymorphisms
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2020.145270

•This study indicated that the AIRE (rs2075876) variant conferred protection against developing SLE disease.•This work revealed no apparent association with the CTLA4 (rs231775) variant and the development of SLE disease.•CTLA4 rs231775 (G/G) genotype observed significant difference with recurrent infection and hematuria. The AIRE (rs2075876) and CTLA4 (rs231775) variants have a crucial function in controlling the negative selection and suppression of T lymphocytes. Numerous reports studied the association of AIRE and CTLA4 variants with different autoimmune disorders, but with inconclusive conclusions. The main purpose of this work is to evaluate the association of these two variants with SLE susceptibility among Egyptian patients. A total of 247 participants (100 SLE patients and 147 healthy controls) were enrolled in this case-controlled study. The genomic DNA of these dual variants was genotyped using the TaqMan genotyping method. The AIRE (rs2075876) variant conferred protection against developing SLE disease under allelic [A allele vs. G allele; OR = 0.16, 95%CI = 0.09–0.28], and dominant [GA + AA vs. GG; OR = 0.14, 95%CI = 0.05–0.34] models. Moreover, patients with AIRE rs2075876 (A/A) genotype revealed a statistically significant with lower levels of complement 3 (p-value = 0.007). Nonetheless, the CTLA4 (rs231775) variant was not associated with increased risk of SLE under all genetic association models (p-value > 0.05). However, CTLA4 rs231775 (G/G) genotype observed significant difference with recurrent infection and hematuria. Our findings indicated that the AIRE (rs2075876) variant conferred protection against developing SLE disease, but not the CTLA4 (rs231775) variant.