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Hair Follicle-Related MicroRNA-34a Serum Expression and rs2666433A/G Variant in Patients with Alopecia: A
Shymaa Ahmed Maher1,2, Nader Ali Ismail3, Eman A Toraih4,5
1Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Abstract:
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 controls—A 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.
Insights
The MIR34A rs2666433 variant is linked to increased alopecia areata (AA) risk and severity. Higher miR-34a levels in circulation are associated with AA pathogenesis and autoimmune comorbidities.
Area of Science:
- Genetics
- Immunology
- Dermatology
Background:
- Alopecia areata (AA) is an immune-mediated hair loss condition.
- MicroRNAs (miRNAs) are implicated in hair follicle biology.
- Single nucleotide polymorphisms (SNPs) can influence gene expression and autoimmune responses.
Purpose of the Study:
- To investigate the association between the MIR34A rs2666433 (A/G) variant and alopecia areata.
- To evaluate the correlation between circulatory miR-34a levels and AA risk, severity, and comorbidities.
Main Methods:
- A case-control study involving 480 participants (240 cases, 240 controls).
- Genotyping of the MIR34A rs2666433 variant using real-time PCR.
- Quantification of serum miR-34a levels via quantitative reverse transcription PCR (qRT-PCR).
Main Results:
- The A allele and A/A genotype of MIR34A rs2666433 were significantly more frequent in AA patients.
- Carriers of the A/A and A/G genotypes had a higher risk of developing AA.
- Serum miR-34a levels were upregulated in AA patients, particularly those with the A/A genotype.
- The heterozygote genotype (A/G) was associated with more severe disease grades and autoimmune comorbidities like SLE and vitiligo.
Conclusions:
- The MIR34A rs2666433 (A/G) variant is a risk factor for alopecia areata.
- Elevated circulatory miR-34a levels may contribute to AA pathogenesis.
- This genetic variant and miRNA levels are associated with disease severity and autoimmune comorbidities.

