Hair Follicle-Related MicroRNA-34a Serum Expression and rs2666433A/G Variant in Patients with Alopecia: A Cross-Sectional Analysis.

Alopecia areata (AA) is a type of immune-mediated alopecia. Recent studies have suggested microRNAs' (miRNAs) implication in several cellular processes, including epidermal and hair follicle biology. Single nucleotide polymorphisms (SNPs) can modify gene expression levels, which may induce an autoimmune response. This case−control study included 480 participants (240 for each case/control group). MicroRNA-34a gene (MIR-34A) rs2666433A/G variant was genotyped using real-time allelic discrimination polymerase chain reaction (PCR). Additionally, circulatory miR-34a levels were quantified by quantitative reverse transcription PCR (qRT-PCR). On comparing between alopecia and non-alopecia cohorts, a higher frequency of A variant was noted among patients when compared to controls­A allele: 28 versus 18% (p < 0.001); A/A genotype: 9 versus 2%; A/G genotype: 39 versus 32% (p < 0.001). A/A and A/G carriers were more likely to develop alopecia under heterozygote comparison (OR = 1.83, 95% CI = 1.14−2.93), homozygote comparison (OR = 4.19, 95% CI = 1.33−13.1), dominant (OR = 2.0, 95% CI = 1.27−3.15), recessive (OR = 3.36, 95% CI = 1.08−10.48), over-dominant (OR = 1.65, 95% CI = 1.04−32.63), and log additive (OR = 1.91, 95% CI = 1.3−2.82) models. Serum miR-34a expression levels were upregulated in alopecia patients with a median and quartile fold change of 27.3 (1.42−2430). Significantly higher levels were more pronounced in A/A genotype patients (p < 0.01). Patients carrying the heterozygote genotype (rs2666433 * A/G) were two times more likely to develop more severe disease grades. Stratified analysis by sex revealed the same results. A high expression level was associated with concomitant autoimmune comorbidities (p = 0.001), in particular SLE (p = 0.007) and vitiligo (p = 0.049). In conclusion, the MIR34A rs2666433 (A/G) variant is associated with AA risk and severity in the studied population. Furthermore, high miR-34a circulatory levels could play a role in disease pathogenesis.

Association of Rs231775 Genetic Variant of Cytotoxic T-lymphocyte Associated Protein 4 with Alopecia Areata Disease in Males: A Case-Control Study.

BACKGROUND: Alopecia Areata (AA) is a common inflammatory immune-mediated non-scarring hair loss; however, the exact genetic susceptibility remains to be clarified. Cytotoxic T-lymphocyte Associated Protein 4 (CTLA4) has emerged as a central and critically important modulator of immune responses and is believed to play a crucial rule in AA pathogenesis. OBJECTIVES: To investigate the association of CTLA4 variant (rs231775) within codon 17 with AA risk and outcomes. METHODS: Genetic analyses of the rs231775 SNP of CTLA4 gene were performed in 186 males (93 AA patients and 93 controls). RESULTS: The rs231775 CTLA4 variant was significantly higher in AA patients in comparison with control subjects especially among heterozygous and dominant model. This association varied significantly with disease severity. CONCLUSIONS: Individuals with homozygosity of rs231775 CTLA4 variant represented AA disease risk and increased severity than their counterparts.Abbreviations: AA: Alopecia areata; CTLA4: Cytotoxic T-lymphocyte Associated Protein 4; SNP: Single nucleotide polymorphism; LADA: Latent autoimmune diabetes in adults; SLE: Systemic lupus erythematosus; SCU: Suez Canal University; SALT: Severity of Alopecia Tool; DNA: Deoxyribonucleic acid; RT-PCR: Real-time polymerase chain reaction, HWE: Hardy-Weinberg equation; RA: rheumatoid arthritis.