A comprehensive association analysis confirms<i>ZMIZ1</i>to be a susceptibility gene for vitiligo in Chinese population

Sun, Yiyuan; Zuo, Xianbo; Zheng, Xiaodong; Zhou, Fusheng; Liang, Bo; Liu, Hong; Chang, Ruixue X.; Gao, Jinping; Sheng, Yujun; Cui, Hongzhou; Wang, Wenjun; Andiappan, Anand Kumar; Rötzschke, Olaf; Yang, Sen; Sun, Liangdan; Zhang, Furen; Zhang, Xuejun; Ren, Yunqing; Li, Jianjun

doi:10.1136/jmedgenet-2013-102233

Cited by 22 publications

(10 citation statements)

References 40 publications

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“…Zhang and co-workers carried out a large GWAS of vitiligo in the Han and Uygur populations of China, detecting complex association signals in the class I and class II regions of the MHC and with the RNASET2-FGFR1OP-CCR6 region of chromosome 6q24 [76]. Deeper analysis of this GWAS [77] detected additional association signals in the region of PMEL , 10q22.1 and a nearby locus suggested to be ZMIZ1 [78], and 11q23.3. Of these associations in Chinese, only that in the RNASET2-FGFR1OP-CCR6 region corresponds to an association detected in Caucasian patients [63].…”

Section: Genomewide Studiesmentioning

confidence: 99%

Genetics of Vitiligo

Spritz¹,

Andersen²

2017

Dermatologic Clinics

144

126

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Synopsis Vitiligo is “complex disorder” (also termed polygenic and multifactorial), reflecting simultaneous contributions of multiple genetic risk factors and environmental triggers. Large-scale genome-wide association studies, principally in European-derived whites and in Chinese, have discovered approximately 50 different genetic loci that contribute to vitiligo risk, some of which also contribute to other autoimmune diseases that are epidemiologically associated with vitiligo. At many of these vitiligo susceptibility loci the corresponding relevant genes have now been identified, and for some of these genes the specific DNA sequence variants that contribute to vitiligo risk are also now known. A large fraction of these genes encode proteins involved in immune regulation, a number of others play roles in cellular apoptosis, and still others are involved in regulating functions of melanocytes. For this last group, there appears to be an opposite relationship between susceptibility to vitiligo and susceptibility to melanoma, suggesting that vitiligo may engage a normal mechanism of immune surveillance for melanoma. While many of the specific biologic mechanisms through which these genetic factors operate to cause vitiligo remain to be elucidated, it is now clear that vitiligo is an autoimmune disease involving a complex relationship between programming and function of the immune system, aspects of the melanocyte autoimmune target, and dysregulation of the immune response.

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Section: Genomewide Studiesmentioning

confidence: 99%

Genetics of Vitiligo

Spritz¹,

Andersen²

2017

Dermatologic Clinics

144

126

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“…Finally, ZMIZ1 (zinc finger MIZ-containing 1) is in the PIAS (protein inhibitor of activated STAT) family of proteins which enhances SMAD signaling in response to TGFβ [38]. In addition to possible effects on osteogenesis, a region containing ZMIZ1 has been associated with inflammatory/autoimmune diseases including Crohn’s disease and ulcerative colitis [39], celiac disease [40], multiple sclerosis [41], and vitiligo [42]. It should be noted that the lower expression of these MSC and iPSC-enriched genes in whole blood does not rule out important functions in low abundance cell types where expression may be significantly higher.…”

Section: Discussionmentioning

confidence: 99%

Generation and differentiation of induced pluripotent stem cells reveal ankylosing spondylitis risk gene expression in bone progenitors

Layh‐Schmitt

Navid

et al. 2016

Clin Rheumatol

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Axial spondyloarthritis (axSpA), which encompasses ankylosing spondylitis, is a complex genetic disease. Aberrant bone formation is a key feature of pathogenesis that can lead to ankylosis of the spine. Our objective is to determine, whether genes whose variants confer susceptibility to AS are expressed in bone progenitors like mesenchymal stem cells (MSCs). Since MSCs from bone marrow is difficult to obtain, we first examined, whether MSCs can be derived from induced pluripotent stem cells (iPSCs). Dermal fibroblasts of two axSpA patients and one healthy control were reprogrammed into iPSCs using a Sendai virus vector encoding pluripotency genes. Pluripotency of iPSCs was examined by embryoid body formation and by testing for stem cell specific gene and protein expression using RT-PCR and immuno fluorescence. iPSCs were differentiated into MSCs by a TGFß inhibitor. MSCs were characterized by flow cytometry using lineage specific antibodies and by their capacity to develop into chondrocytes, adipocytes, and osteoblasts in lineage-specific medium. RNA-seq was applied to determine genome-wide gene expression patterns in MSCs, iPSCs, and blood. We show for the first time, that expression levels of several AS susceptibility genes (EDIL3, ANO6, HAPLN1, ANTXR2) involved in bone formation are significantly elevated in MSCs (2–15-fold; p ≤ 0.05) compared to blood or iPSCs and demonstrate that iPSC-derived MSCs can be differentiated into osteoblasts, chondrocytes, and adipocytes. We conclude, MSCs generated from patient fibroblast-derived iPSC lines are useful tools for studying functional genomics of risk genes associated with bone formation in AS pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s10067-016-3469-5) contains supplementary material, which is available to authorized users.

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“…Polymorphisms in non-immune-related genes have also been identified as risk factors. The melanocyte-specific genes (TYR, PMEL, MC1R, OCA2) encode for proteins or enzymes that participate in melanin production, and the ZMIZI gene is involved in the regulation of melanocyte development and survival (Sun et al 2014). Genetic variants of these genes may serve as T cell antigens (autoantigens) which facilitates the initiation of an anti-melanocyte immune response contributing to cellular stress and melanocyte damage resulting in the development of vitiligo (Jin et al 2010;Spritz 2013).…”

Section: Genetic Susceptibilitymentioning

confidence: 99%

Exploring vitiligo susceptibility and management: a brief review

Rahman

Hasija

2018

biomed dermatol

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Background: Vitiligo is a common dermatological disorder of chronic depigmentation which is phenotypically characterized by white macules on the skin caused as a result of the systematic destruction of functional melanocytes. This review provides an overview of vitiligo, its etiopathogenesis and disease management, and also discusses the scope of network-interaction studies and polypharmacological studies in understanding vitiligo disease module. Methods: A narrative review of the relevant published literatures known to the authors that comprehensively discussed about vitiligo and its implications was conducted. Results: Emerging evidence underlines the existing connection between deregulated miRNA function and vitiligo pathogenesis. It has also been linked with autoimmunity for the cause of melanocyte death in susceptible individuals. Alteration of genetic factors involved in immune responses and melanogenesis along with environmental factors are central to disease manifestation. Screening methods as such are not available for vitiligo, and the diagnosis is based on the assessment of the absence of melanocytes from the lesions in the affected area. With the occurrence of vitiligo at any age, most people typically develop it at a young age. Depending on the disease course and duration, clinical management primarily involves disease stabilization either by repigmentation or depigmentation of the skin. Conclusions: Several questions remain unsolved which indeed makes vitiligo an excellent model for studying autoimmune and degenerative processes. An understanding of the underlying degenerative mechanisms and unraveling the biological mediators of melanocyte loss will open up avenues for testing novel therapeutic approaches in vitiligo management. Such studies can revolutionize our apprehension of the molecular interconnections that underpin vitiligo pathogenesis.

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A comprehensive association analysis confirmsZMIZ1to be a susceptibility gene for vitiligo in Chinese population

Abstract: Our study has confirmed ZMIZ1 as a novel susceptibility locus for vitiligo and further suggested rs1408944 to be the putative causal variant that potentially interrupts TF binding and thus the transcriptional regulation of ZMIZ1.

Cited by 22 publications

References 40 publications

Genetics of Vitiligo

Genetics of Vitiligo

Generation and differentiation of induced pluripotent stem cells reveal ankylosing spondylitis risk gene expression in bone progenitors

Exploring vitiligo susceptibility and management: a brief review

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