Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo

Jin, Ying; Birlea, Stanca A.; Fain, Pamela R.; Ferrara, Tracey M.; Ben, Songtao; Riccardi, Sheri L.; Cole, Joanne B.; Gowan, Katherine; Holland, Paulene J.; Bennett, Dorothy C.; Luiten, Rosalie M.; Wolkerstorfer, Albert; Veen, J.P.W. van der; Hartmann, Anke; Eichner, Saskia; Schuler, Gerold; Geel, Nanja van; Lambert, Jo; Kemp, E. Helen; Gawkrodger, David J.; Weetman, Anthony P.; Taı̈eb, Alain; Jouary, Thomas; Ezzedine, Khaled; Wallace, Margaret R.; McCormack, Wayne T.; Picardo, Mauro; Leone, Giovanni; Overbeck, Andreas; Silverberg, Nanette B.; Spritz, Richard A.

doi:10.1038/ng.2272

Cited by 296 publications

(255 citation statements)

References 62 publications

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“…Consistent with the critical functions of Bach2 in the immune cells, genome-wide association studies (GWAS) suggest the involvement of Bach2 in the development of diverse immune system-related diseases, such as generalized vitiligo (Jin et al 2012), asthma (Ferreira et al 2011b), type 1 diabetes (Cooper et al 2008;Plagnol et al 2011), type 2 diabetes (Lee et al 2011), Crohn's disease Christodoulou et al 2013) and celiac disease (Dubois et al 2010). The utilization of Bach2-deficient mice in disease models related to these human diseases is expected to provide insight into the causal links and mechanistic basis of these conditions.…”

Section: Association Between Bach2 and Immune-related Human Diseasesmentioning

confidence: 86%

Wearing Red for Signaling: The Heme-Bach Axis in Heme Metabolism, Oxidative Stress Response and Iron Immunology

Igarashi

Watanabe-Matsui

2014

Tohoku J. Exp. Med.

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The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of "iron immunology" as the synthesis of the iron metabolism and the immune response.

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Section: Association Between Bach2 and Immune-related Human Diseasesmentioning

confidence: 86%

Wearing Red for Signaling: The Heme-Bach Axis in Heme Metabolism, Oxidative Stress Response and Iron Immunology

Igarashi

Watanabe-Matsui

2014

Tohoku J. Exp. Med.

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“…GISTIC results were downloaded through web APIs invoked in MATLAB. We computed the percentage of gains and deletions events and report the two most frequently altered genes for each cancer of interest [66][67][68][69][70][71][72][73][74][75][76][77][78][79].…”

Section: Basal Determinantsmentioning

confidence: 99%

Cancer Stem Cell Division: When the Rules of Asymmetry Are Broken

Mukherjee

Kong

Brat³

2015

Stem Cells and Development

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Asymmetric division of stem cells is a highly conserved and tightly regulated process by which a single stem cell produces two daughter cells and simultaneously directs the differential fate of both: one retains its stem cell identity while the other becomes specialized and loses stem cell properties. Coordinating these events requires control over numerous intra-and extracellular biological processes and signaling networks. In the initial stages, critical events include the compartmentalization of fate determining proteins within the mother cell and their subsequent passage to the appropriate daughter cell. Disturbance of these events results in an altered dynamic of self-renewing and differentiation within the cell population, which is highly relevant to the growth and progression of cancer. Other critical events include proper asymmetric spindle assembly, extrinsic regulation through micro-environmental cues, and noncanonical signaling networks that impact cell division and fate determination. In this review, we discuss mechanisms that maintain the delicate balance of asymmetric cell division in normal tissues and describe the current understanding how some of these mechanisms are deregulated in cancer.The universe is asymmetric and I am persuaded that life, as it is known to us, is a direct result of the asymmetry of the universe or of its indirect consequences. The universe is asymmetric.-Louis Pasteur

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“…[40] In addition, melanocyte-specific genes have also been associated with increased risk, including OCA2, MC1R and TYR, which are thought to be the source of melanocyte-specific antigens. [42] Oxidative stress and vitiligo A constant factor in many hypotheses regarding the pathobiology of vitiligo is the involvement of oxidative stress. Studies have suggested that individuals with vitiligo have a compromised antioxidant response, [43] with enzymes such as catalase and superoxide dismutase present at higher than expected levels in tissue from perilesional areas and in sera from patients with vitiligo.…”

Section: Aetiologymentioning

confidence: 99%

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

et al. 2013

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The primary pigment that determines human skin, hair and eye colour is melanin, which is synthesised by melanocytes. Melanin protects the skin from ultraviolet (UV) radiation and there is an inverse correlation between the degree of constitutive pigmentation and the risk of sun-induced skin cancers. Besides the life-threatening cancer risk, loss of pigmentation results in premature aging, compromised cutaneous immunity and significant emotional distress to affected individuals. [1][2][3] During embryonic development, melanocyte precursors that arise from the neural crest populate several areas including the interfollicular epidermis and hair follicle bulge in the skin; the uveal tract of the eye; and the stria vascularis, vestibular apparatus and endolymphatic sac of the ear. The development of melanocytes is tightly regulated at the genetic level by a number of genes that control proliferation, survival and migration of precursor cells to the various sites of the body and their differentiation into active melanocytes. A key regulator of this process is the microphthalmia transcription factor (MITF), which has been dubbed the 'master regulator' of the melanocyte, capable of modulating expression of several melanocytespecific proteins.[4] MITF mutations result in Waardenburg syndrome type II.[5] Once the melanocyte has differentiated, MITF regulates expression of genes in response to UV exposure, facilitating the tanning response.Melanocytes produce two forms of melanin, black-brown eumelanin and red-yellow pheomelanin. Skin and hair colour Corresponding author: P Manga (prashiela.manga@nyumc.org)Pigmentation disorders span the genetic spectrum from single-gene autosomal recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA connotes a group of disorders that result in hypopigmented skin due to decreased melanin production in melanocytes and loss of visual acuity. There are four non-syndromic forms, OCA1-4, which are classified based on the gene that is mutated (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively). Despite the fact that multiple genes account for the various forms of OCA, the phenotypes of all four forms result from disruption in the maturation and trafficking of the enzyme tyrosinase. OCA2 is the most prevalent autosomal recessive disorder among southern African blacks, affecting 1/3 900 individuals; while OCA3, although rare, is most prevalent in southern Africa. Another common pigmentation disorder in southern Africa is vitiligo, which affects 1 -2% of people worldwide. Vitiligo is a complex, acquired disorder in which melanocytes are destroyed due to an autoimmune response. The aetiology underlying this disorder is poorly understood, although recent genetic association studies have begun to shed light on the contributing factors. Pigmentation disorders have significant psychosocial implications and co-morbidities, yet therapies are still lacking. Recent progress in...

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Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo

Cited by 296 publications

References 62 publications

Wearing Red for Signaling: The Heme-Bach Axis in Heme Metabolism, Oxidative Stress Response and Iron Immunology

Wearing Red for Signaling: The Heme-Bach Axis in Heme Metabolism, Oxidative Stress Response and Iron Immunology

Cancer Stem Cell Division: When the Rules of Asymmetry Are Broken

Biology and genetics of oculocutaneous albinism and vitiligo – common pigmentation disorders in southern Africa

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