Recent Progress in the Genetics of Generalized Vitiligo

Overview

Journal J Genet Genomics

Publisher Science Press

Specialty Genetics

Date 2011 Jul 23

PMID 21777851

Citations 23

Authors

Richard A Spritz

Affiliations

Soon will be listed here.

Abstract

Vitiligo is an acquired disease characterized principally by patchy depigmentation of skin and overlying hair. Generalized vitiligo (GV), the predominant form of the disorder, results from autoimmune loss of melanocytes from affected regions. GV is a "complex trait", inherited in a non-Mendelian polygenic, multifactorial manner. GV is epidemiologically associated with other autoimmune diseases, both in GV patients and in their close relatives, suggesting that shared genes underlie susceptibility to this group of diseases. Early candidate gene association studies yielded a few successes, such as PTPN22, but most such reports now appear to be false-positives. Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies (GWAS) of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes. Together, these genes highlight biological systems and pathways that reach from the immune cells to the melanocyte, and provide insights into both disease pathogenesis and potential new targets for both treatment and even prevention of GV and other autoimmune diseases in genetically susceptible individuals.

Citing Articles

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References

Spritz R . The genetics of generalized vitiligo. Curr Dir Autoimmun. 2008; 10:244-57. DOI: 10.1159/000131501. View

Liang Y, Yang S, Zhou Y, Gui J, Ren Y, Chen J . Evidence for two susceptibility loci on chromosomes 22q12 and 6p21-p22 in Chinese generalized vitiligo families. J Invest Dermatol. 2007; 127(11):2552-7. DOI: 10.1038/sj.jid.5700904. View

Le Poole I, Sarangarajan R, Zhao Y, Stennett L, Brown T, Sheth P . 'VIT1', a novel gene associated with vitiligo. Pigment Cell Res. 2002; 14(6):475-84. PMC: 1747534. DOI: 10.1034/j.1600-0749.2001.140608.x. View

Ongenae K, van Geel N, Naeyaert J . Evidence for an autoimmune pathogenesis of vitiligo. Pigment Cell Res. 2003; 16(2):90-100. DOI: 10.1034/j.1600-0749.2003.00023.x. View

Kemp E, Gavalas N, Gawkrodger D, Weetman A . Autoantibody responses to melanocytes in the depigmenting skin disease vitiligo. Autoimmun Rev. 2007; 6(3):138-42. DOI: 10.1016/j.autrev.2006.09.010. View

Gross A, Tapia F, Mosca W, Perez R, Briceno L, Henriquez J . Mononuclear cell subpopulations and infiltrating lymphocytes in erythema dyschromicum perstans and vitiligo. Histol Histopathol. 1987; 2(3):277-83. View

Al-Fouzan A, Al-Arbash M, Fouad F, Kaaba S, Mousa M . Study of HLA class I/IL and T lymphocyte subsets in Kuwaiti vitiligo patients. Eur J Immunogenet. 1995; 22(2):209-13. DOI: 10.1111/j.1744-313x.1995.tb00232.x. View

Birlea S, Fain P, Spritz R . A Romanian population isolate with high frequency of vitiligo and associated autoimmune diseases. Arch Dermatol. 2008; 144(3):310-6. DOI: 10.1001/archderm.144.3.310. View

Kingo K, Philips M, Aunin E, Luuk H, Karelson M, Ratsep R . MYG1, novel melanocyte related gene, has elevated expression in vitiligo. J Dermatol Sci. 2006; 44(2):119-22. DOI: 10.1016/j.jdermsci.2006.08.001. View

10.

Alkhateeb A, Fain P, Spritz R . Candidate functional promoter variant in the FOXD3 melanoblast developmental regulator gene in autosomal dominant vitiligo. J Invest Dermatol. 2005; 125(2):388-91. DOI: 10.1111/j.0022-202X.2005.23822.x. View

11.

Liu J, Li M, Chen H, Zhong S, Yang S, Du W . Association of vitiligo with HLA-A2: a meta-analysis. J Eur Acad Dermatol Venereol. 2007; 21(2):205-13. DOI: 10.1111/j.1468-3083.2006.01899.x. View

12.

Zurawek M, Fichna M, Januszkiewicz-Lewandowska D, Gryczynska M, Fichna P, Nowak J . A coding variant in NLRP1 is associated with autoimmune Addison's disease. Hum Immunol. 2010; 71(5):530-4. DOI: 10.1016/j.humimm.2010.02.004. View

13.

Spritz R . The genetics of generalized vitiligo: autoimmune pathways and an inverse relationship with malignant melanoma. Genome Med. 2010; 2(10):78. PMC: 2988443. DOI: 10.1186/gm199. View

14.

Birlea S, Jin Y, Bennett D, Herbstman D, Wallace M, McCormack W . Comprehensive association analysis of candidate genes for generalized vitiligo supports XBP1, FOXP3, and TSLP. J Invest Dermatol. 2010; 131(2):371-81. PMC: 3172683. DOI: 10.1038/jid.2010.337. View

15.

Quan C, Ren Y, Xiang L, Sun L, Xu A, Gao X . Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Nat Genet. 2010; 42(7):614-8. DOI: 10.1038/ng.603. View

16.

Hirschhorn J, Lohmueller K, Byrne E, Hirschhorn K . A comprehensive review of genetic association studies. Genet Med. 2002; 4(2):45-61. DOI: 10.1097/00125817-200203000-00002. View

17.

Tastan H, Akar A, Orkunoglu F, Arca E, Inal A . Association of HLA class I antigens and HLA class II alleles with vitiligo in a Turkish population. Pigment Cell Res. 2004; 17(2):181-4. DOI: 10.1111/j.1600-0749.2004.00141.x. View

18.

Jin Y, Birlea S, Fain P, Mailloux C, Riccardi S, Gowan K . Common variants in FOXP1 are associated with generalized vitiligo. Nat Genet. 2010; 42(7):576-8. PMC: 2893242. DOI: 10.1038/ng.602. View

19.

Jin Y, Birlea S, Fain P, Gowan K, Riccardi S, Holland P . Genome-wide analysis identifies a quantitative trait locus in the MHC class II region associated with generalized vitiligo age of onset. J Invest Dermatol. 2011; 131(6):1308-12. PMC: 3172680. DOI: 10.1038/jid.2011.12. View

20.

Ogg G, Dunbar P, Romero P, Chen J, Cerundolo V . High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J Exp Med. 1998; 188(6):1203-8. PMC: 2212532. DOI: 10.1084/jem.188.6.1203. View