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East Lansing, MI, United States

Coda A.B.,Center for Investigative Dermatology | Sinha A.A.,State University of New York at Buffalo
Genomics | Year: 2011

Alopecia areata (AA), a non-scarring inflammatory hair loss disorder, is a complex disease determined by genetic and environmental factors that remain largely unknown. Re-analysis of genome-wide microarray data in 9 patient blood and 10 skin samples revealed transcriptional "hot spots" at chromosomes 1q21-q32, 11q12-q14, and 16p13-p13.3 (blood) and 6p21.3, 12q12-q13, and 17q12-q24 (skin) harboring high densities of dysregulated genes. We then integrated AA associated gene expression profiles with previous genome-wide genetic analyses to identify a subset of 112 dysregulated genes that map to putative susceptibility loci. Finally, we analyzed AA patients stratified by defined clinical characteristics, including a history of atopy, autoimmune disease, and nail disease, thus deconstructing the clinical heterogeneity observed among AA patients. Integrated chromosomal and transcriptional profiling identified several dysregulated chromosomal regions and genes representing an enriched set of biomarkers relevant to AA pathogenesis and clinical heterogeneity. © 2011 Elsevier Inc. Source

Subramanya R.D.,Center for Investigative Dermatology | Coda A.B.,Center for Investigative Dermatology | Sinha A.A.,Center for Investigative Dermatology
Genomics | Year: 2010

Alopecia areata (AA) is a non-scarring inflammatory hair loss disease with a complex autoimmune etiopathogenesis that is poorly understood. In order to investigate the pathogenesis of AA at the molecular level, we examined the gene expression profiles in skin samples from lesional (n= 10) and non-lesional sites (n= 10) of AA patients using Affymetrix Hu95A-v2 arrays. 363 genes were found to be differentially expressed in AA skin compared to non-lesional skin; 97 were up-regulated and 266 were down-regulated. Functional classification of the differentially expressed genes (DEGs) provides evidence for T-cell mediated immune response (CCL5, CXCL10, CD27, ICAM2, ICAM3, IL7R, and CX3CL1), and a possible humoral mechanism (IGHG3, IGHM, and CXCR5) in AA. We also find modulation in gene expression favoring cellular proliferation arrest at various levels (FGF5, FGF18, EREG, and FOXC2) with apoptotic dysregulation (LCK, TNF, TRAF2, and SFN) and decreased expression of hair follicle structural proteins. Further analysis of patients with AAT (< 1. year duration, n= 4) and AAP (> 1. year duration, n= 6) of disease revealed 262 DEGs distinctly separating the 2 groups, indicating the existence of gene profiles unique to the initial and later stages of disease. © 2010 Elsevier Inc. Source

Coda A.B.,Center for Investigative Dermatology | Hysa V.Q.,Center for Investigative Dermatology | Seiffert-Sinha K.,Center for Investigative Dermatology | Sinha A.A.,Center for Investigative Dermatology
Genes and Immunity | Year: 2010

Alopecia areata (AA) is an autoimmune hair loss disorder in which systemic disturbances have been described, but are poorly understood. To evaluate disease mechanisms, we examined gene expression in the blood of defined clinical subgroups (patchy AA persistent type, AAP, n5; alopecia universalis, AU, n4) and healthy controls (unaffected relatives, UaR, n5; unaffected non-relatives, UaNR, n4) using microarrays. Unsupervised hierarchical clustering separates all four patient and control groups, producing three distinct expression patterns reflective of inheritance, disease and severity signatures. Functional classification of differentially expressed genes (DEGs) comparing disease (AAP, AU) vs normal (UaR) groups reveals upregulation in immune response, cytokine signaling, signal transduction, cell cycle, proteolysis and cell adhesion-related genes. Pathway analysis further reveals the activation of several genes related to natural killer-cell cytotoxicity, apoptosis, mitogen activated protein kinase, Wnt signaling and B- and T-cell receptor signaling in AA patients. Finally, 35 genes differentially expressed in AA blood overlap with DEGs previously identified in AA skin lesions. Our results implicate innate and adaptive immune processes while also revealing novel pathways, such as Wnt signaling and apoptosis, relevant to AA pathogenesis. Our data suggest that peripheral blood expression profiles of AA patients likely carry new biomarkers associated with disease susceptibility and expression. © 2010 Macmillan Publishers Limited All rights reserved. Source

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