Tru9I Variant as a Novel Genetic Marker for Vitamin D Deficiency in Alopecia Areata

Ghadah Alhetheli,1 Mohammed Saleh Al-Dhubaibi,2 Saleh Salem Bahaj,3 Sharif Alhajlah,4 Ahmed Ibrahim AbdElneam5,6 1Department of Dermatology, College of Medicine, Qassim University, Buraydah, Saudi Arabia; 2Departments of Dermatology, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia; 3Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a, Yemen; 4Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra, 11961, Saudi Arabia; 5Department of Clinical Biochemistry, Department of Basic Medical Sciences, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia; 6Molecular Genetics and Enzymology Department, Human Genetics and Genome Research Institute, National Research Center, Cairo, 12622, EgyptCorrespondence: Saleh Salem Bahaj, Department of Microbiology and Immunology Faculty of Medicine and Health Sciences Sana’a University, Sana’a, Yemen, Tel +967711221188, Email [email protected]: Alopecia areata (AA), is a common autoimmune nonscarring alopecia. Vitamin D is involved in various biological processes such as immune regulation, cellular growth, and specialization, as well as the maintenance of the hair cycle. We aimed to explore the impact of different Tru9I variant genotypes on serum vitamin D levels and vitamin D receptor (VDR) gene expression.Methods: Case–control study that included 72 individuals diagnosed with AA, along with age and sex matched healthy controls of 72 individuals. Blood samples were obtained to measure Vitamin D level and VDR gene expression focusing on Tru9I variant genotypes.Results: Our findings indicate, for the first time, a possible association between the “U” allele and low vitamin D levels, along with altered activity of the VDR gene as observed in patients with AA.Conclusion: This suggests a complex causal relationship between genetic factors and vitamin D in AA. Interestingly, “u” allele was found to be significantly more prevalent in the healthy control group than in the patients group, raising the possibility of its protective mechanism against the development of this disease in healthy individuals.Keywords: Tru9I variant, vitamin D, VDR gene expression, alopecia areat

Identification of Upregulating Genes, Transcription Factors, and miRNAs in Vitiligo. In silico Study

Ahmed Ibrahim AbdElneam,1,2 Mohammed Saleh Al-Dhubaibi,3 Saleh Salem Bahaj,4 Ghada Farouk Mohammed,5 Lina Mohammed Atef5 1Department of Clinical Biochemistry, Department of Basic Medical Sciences, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia; 2Molecular Genetics and Enzymology Department, Human Genetics and Genome Research Institute, National Research Center, Cairo, Egypt; 3Departments of Dermatology, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia; 4Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a, Yemen; 5Department of Dermatology, Venereology, and Sexology, Faculty of Medicine, Suez Canal University, Ismailia, EgyptCorrespondence: Saleh Salem Bahaj, Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Sana’a University, Yemen, Email [email protected]: Depigmentation of specific areas of the skin is a persistent and long-lasting dermatologic disorder known as vitiligo, stemming from the impairment and disruption of melanocytes both structurally and functionally, leading to the loss of pigmentation in those regions.Aim: Our objective was to identify the pivotal genes and upstream regulators, transcription factors (TFs), microRNAs (miRNAs), and pathways implicated in the pathogenesis of vitiligo.Methods: An integrated analysis was conducted using microarray datasets on vitiligo obtained from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were additionally investigated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Various bioinformatics approaches were utilized, making use of publicly accessible databases to identify appropriate TFs and miRNAs.Results: Our investigation identified TYR, MLANA, TYRP1, PMEL, OCA2, SLC45A2, GPR143, DCT, TRPM1, and EDNRB as the most appropriate genes associated with vitiligo. Our suggestion is that the identified biological processes include developmental pigmentation (GO:0048066) and pigment metabolic processes (GO:0042440) as the most suitable biological processes. In contrast, the KEGG pathways that showed significance in our analysis are Tyrosine metabolism (Path: hsa00350) and Melanogenesis (Path: hsa04916). We hypothesized the involvement of ten TFs and 73 miRNAs in the regulation of genes related to vitiligo.Conclusion: TYR, MLANA, TYRP1, PMEL, OCA2, SLC45A2, GPR143, DCT, TRPM1, and EDNRB are the top ten genes that are pivotal in the progression and exhibition of vitiligo. The biological, cellular, molecular, and KEGG pathways of those genes has an imperative role in the pathogenesis of vitiligo. TFs and miRNAs that interact with this gene are listed, shedding light on the regulatory mechanisms governing the expression of these key genes in vitiligo.Keywords: Vitiligo, miRNAs, transcription factors, microarray, DEGs, GE