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

Saleh A Alghamdi; Shahad W Kattan; Eman A Toraih; Majed G Alrowaili; Manal S Fawzy; Rami M Elshazli

doi:10.1016/j.gene.2020.145270

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

Gene. 2021 Feb 5:768:145270. doi: 10.1016/j.gene.2020.145270. Epub 2020 Oct 26.

Authors

Saleh A Alghamdi¹, Shahad W Kattan², Eman A Toraih³, Majed G Alrowaili⁴, Manal S Fawzy⁵, Rami M Elshazli⁶

Affiliations

¹ Medical Genetics, Clinical Laboratory Department, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia. Electronic address: G.saleh@tu.edu.sa.
² Department of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia.
³ Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA; Genetics Unit, Histology and Cell Biology Department, Faculty of Medicine, Suez Canal University, Egypt.
⁴ Department of Surgery (Orthopedic Division), Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
⁵ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
⁶ Biochemistry and Molecular Genetics Unit, Department of Basic Sciences, Faculty of Physical Therapy, Horus University - Egypt, New Damietta 34518, Egypt. Electronic address: Relshazly@horus.edu.eg.

PMID: 33122082
DOI: 10.1016/j.gene.2020.145270

Abstract

Background: 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.

Subjects and methods: 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.

Results: 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.

Conclusions: Our findings indicated that the AIRE (rs2075876) variant conferred protection against developing SLE disease, but not the CTLA4 (rs231775) variant.

Keywords: AIRE (rs2075876); CTLA4 (rs231775); Genetic polymorphisms; SLE.

MeSH terms

AIRE Protein
Adult
CTLA-4 Antigen / genetics*
Case-Control Studies
Egypt
Female
Gene Frequency / genetics
Genetic Association Studies
Genetic Predisposition to Disease / genetics*
Genome / genetics
Genotype
Humans
Lupus Erythematosus, Systemic / genetics*
Male
Polymorphism, Single Nucleotide / genetics
Transcription Factors / genetics*

Substances

CTLA-4 Antigen
CTLA4 protein, human
Transcription Factors