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Interactome analysis of gene expression profile reveals potential novel key transcriptional regulators of skin pathology in vitiligo

Genes & Immunity volume 17, pages 30–45 (2016)Cite this article

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Abstract

Selective destruction of epidermal melanocytes is central to vitiligo (VL), a common acquired, autoimmune depigmentory disorder of the skin. Like other autoimmune diseases, the pathogenesis of VL is obscure and both multifactorial and polygenic. The prevailing theory is that VL may be part of an autoimmune diathesis. To evaluate mechanisms underlying disease development and progression, we studied genome-wide gene expression from lesional and non-lesional skin of patients with non-segmental VL. Unbiased clustering and principal components analyses reveals a 'lesional pathology'-based signature. Pathway-based analyses of the differentially expressed genes underscore processes such as melanocyte development and cell cycle as central drivers of the disease state. Interactome analysis identifies several key transcriptional regulators potentially affecting disease pathogenesis both within and 'hidden' from the data set. Finally, two genes within six identified transcriptional 'hot spots' coincide with previous VL-associated genetic elements. The remaining genes in the 'hot spots' offer an additional set of potential disease-linked loci that may help to guide future studies aimed at identifying disease risk genes.

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Acknowledgements

We thank BK Sinha and M Sinha for continued guidance and support. This work was supported in part through grants to AAS from the National Vitiligo Foundation and the American Vitiligo Research Foundation.

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  1. Department of Dermatology, University at Buffalo, 6078 Clinical and Translational Research Center, Buffalo, NY, USA

    R Dey-Rao & A A Sinha

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Dey-Rao, R., Sinha, A. Interactome analysis of gene expression profile reveals potential novel key transcriptional regulators of skin pathology in vitiligo. Genes Immun 17, 30–45 (2016). https://doi.org/10.1038/gene.2015.48

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