Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Biomolecules. 2022 Apr 19;12(5):602. doi: 10.3390/biom12050602.
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.
斑秃（AA）是一种免疫介导的脱发。最近的研究表明，微 RNA（miRNAs）在包括表皮和毛囊生物学在内的几个细胞过程中具有重要作用。单核苷酸多态性（SNP）可以改变基因表达水平，从而可能引发自身免疫反应。本病例对照研究纳入了 480 名参与者（病例组和对照组各 240 名）。采用实时等位基因鉴别聚合酶链反应（PCR）对微 RNA-34a 基因（MIR-34A）rs2666433A/G 变异进行基因分型。此外，通过定量逆转录 PCR（qRT-PCR）定量循环 miR-34a 水平。在比较脱发组和非脱发组时，与对照组相比，患者中 A 变体的频率更高——A 等位基因：28%比 18%（p<0.001）；AA 基因型：9%比 2%；AG 基因型：39%比 32%（p<0.001）。与杂合子相比，A/A 和 A/G 携带者更有可能患上脱发（OR=1.83，95%CI=1.14-2.93），与纯合子相比（OR=4.19，95%CI=1.33-13.1），显性（OR=2.0，95%CI=1.27-3.15），隐性（OR=3.36，95%CI=1.08-10.48），超显性（OR=1.65，95%CI=1.04-32.63）和对数相加（OR=1.91，95%CI=1.3-2.82）模型。脱发患者血清 miR-34a 表达水平上调，中位数和四分位距倍数变化为 27.3（1.42-2430）。A/A 基因型患者的水平明显更高（p<0.01）。携带杂合子基因型（rs2666433*A/G）的患者发生更严重疾病等级的可能性增加了两倍。按性别分层分析得到了相同的结果。高水平表达与同时发生的自身免疫性合并症相关（p=0.001），特别是 SLE（p=0.007）和白癜风（p=0.049）。总之，在研究人群中，MIR34A rs2666433（A/G）变体与 AA 风险和严重程度相关。此外，循环 miR-34a 水平升高可能在疾病发病机制中起作用。
