Association of Autoimmune Regulator Gene Rs2075876 Variant, but Not Gene Expression with Alopecia Areata in Males: A Case–control Study

ABSTRACT

Alopecia areata (AA) is a non-scarring hair loss of autoimmune etiology. The autoimmune regulator (AIRE) gene is believed to be an important driver in AA pathogenesis. Genetic variants can alter mRNA expression levels which may provoke an autoimmune response. A total of 337 males (97 AA patients and 240 controls) were enrolled in the current case–control study. On screening of the most frequent variants in the gene, rs2075876 (A/G) polymorphism in intron 5 was selected and genotyped using Real-Time PCR (polymerase chain reaction) technology. Additionally, circulatory AIRE expression levels were quantified by quantitative reverse-transcription PCR (qRT-PCR). Allelic discrimination analysis revealed GG genotype to be more frequent in patients (90.7% in AA compared to 32.5% in controls, p < .001). G variant conferred increased risk to alopecia under homozygote comparison (GG versus AA: OR = 16.1, 95%CI = 5.57–46.3), dominant model (GG+AG versus AA: OR = 7.24, 95%CI = 2.5–20.5), recessive model (GG versus AG+AA: OR = 20.3, 95%CI = 9.7–42.4), and allelic model (G versus A: OR = 11.6, 95%CI = 6.47–21.1). The expression levels of AIRE gene did not differ significantly between patients and controls and were not related to rs2075876 variant. In conclusion, the intronic variant (rs2075876) is suggested to be a potent susceptibility variant for AA development in the studied population.

Abbreviations: AA: Alopecia areata; AIRE: Autoimmune Regulator; APECED: Autoimmune, Polyendocrinopathy Candidiasis Ectodermal Dystrophy; DLQI: Dermatology life quality index questionnaire; MIQE: Minimum information for publication of quantitative real-time PCR experiments; mTEC: Medullary thymic epithelial cells; PHD: Plant homeodomain; qRT-PCR: Quantitative reversetranscription-polymerase chain reaction; RA: Rheumatoid arthritis

KEYWORDS:

• Alopecia areata
• autoimmune regulator
• polymorphism
• gene expression
• Egyptians

Acknowledgments

The authors thank the Center of Excellence in Molecular and Cellular Medicine, Suez Canal University, Ismailia, Egypt for providing the facilities for performing the research work as well as we thank all participants who agree to participate in the current study.

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All data and material related to the present work have been included in this article.

Ethics approval and consent to participate

The study received ethical approval (No. 3499) from the board of the Ethics Committee of Faculty of Medicine, Suez Canal University. Informed consent was obtained from all participants.

Consent for publication

Has been taken from the specified patients.

Competing interests

No potential conflict of interest was reported by the authors.

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No sources of funding were used for this work.