Document Type : Review article

Authors

1 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

2 Social Health Determinants Research Center, Shahrekord University of Medical Sciences, Shahrekrod, I.R. Iran.

3 Skin Disease and Leishmaniasis Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.

4 Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Background: Vitiligo is an acquired, idiopathic, and common depigmentation disorder of the skin that affects people of all ages and both sexes equally in the worldwide. Although etiology of the disease is unknown, there are theories such as environment and genetic factors.
Methods: In this article, we collected and summarized the appropriate manuscripts regarding the epidemiology and genetics by using the terms vitiligo and genetic epidemiology in PubMed and Google scholar.
Results: Studies showed the highest prevalence of disease in African countries, but with regard to distribute disease in different areas, environmental factors are as other causes of vitiligo and three genes FOXP3, XBP1 and TSLP had the most association with the disease.
Conclusion: It seems that recognition of the genetic base of vitiligo will supply new insight therapies for its. Therefore, more genetic studies are needed to discover the genes and causes linked to clinical aspects of this disease.

Keywords

Main Subjects

1.Mulekar SV, Isedeh P. Surgical interventions for vitiligo: an evidence-based review. Br J Dermatol. 2013;169 Suppl 3:57- 66. doi: 10.1111/bjd.12532. 
2.Manga P, Elbuluk N, Orlow SJ. Recent advances in understanding vitiligo. F1000Res. 2016;5. doi: 10.12688/ f1000research.8976.1. 
3.Metwalley KA, Farghaly HS. Hepatitis C virus infection in a child with autoimmune polyendocrine syndrome type 2: a case report. J Med Case Rep. 2012;6:221. doi: 10.1186/1752- 1947-6-221. 
4.Alzolibani AA, Al Robaee A, Zedan KH. Genetic epidemiology and heritability of vitiligo. Vitiligo-Management and Therapy. InTech; 2011. doi: 10.5772/25502. 
5.Le Poole IC, Das PK, van den Wijngaard RM, Bos JD, Westerhof W. Review of the etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol. 1993;2(4):145-53. 
6.AlGhamdi KM, Kumar A. Depigmentation therapies for normal skin in vitiligo universalis. J Eur Acad Dermatol Venereol. 2011;25(7):749-57. doi: 10.1111/j.1468-3083.2010.03876.x. 
7.Dahl MV. Imiquimod: a cytokine inducer. J Am Acad Dermatol. 2002;47(4 Suppl):S205-8. 
8.Aslanian FM, Noe RA, Antelo DP, Farias RE, Das PK, Galadari I, et al. Immunohistochemical findings in active vitiligo including depigmenting lesions and non-lesional skin. Open Dermatol J. 2008;2:105-10. doi: 10.2174/1874372200802010105. 
9.Whitton ME, Ashcroft DM, Gonzalez U. Therapeutic interventions for vitiligo. J Am Acad Dermatol. 2008;59(4):713- 7. doi: 10.1016/j.jaad.2008.06.023. 
10.Ghafourian E, Ghafourian S, Sadeghifard N, Mohebi R, Shokoohini Y, Nezamoleslami S, et al. Vitiligo: Symptoms, Pathogenesis and Treatment. Int J Immunopathol Pharmacol. 2014;27(4):485-9. doi: 10.1177/039463201402700403. 
11.Olsson MJ, Juhlin L. Transplantation of melanocytes in vitiligo. Br J Dermatol. 1995;132(4):587-91. 
12.Sigmon JR, Yentzer BA, Feldman SR. Calcitriol ointment: a review of a topical vitamin D analog for psoriasis. J Dermatolog Treat. 2009;20(4):208-12. doi: 10.1080/09546630902936810. 
13.Siadat AH, Zeinali N, Iraji F, Abtahi-Naeini B, Nilforoushzadeh MA, Jamshidi K, et al. Narrow-band ultraviolet B versus oral minocycline in treatment of unstable vitiligo: a prospective comparative trial. Dermatol Res Pract. 2014;2014:240856. doi: 10.1155/2014/240856. 
14.Behl PN. Treatment of vitilgo with homologous thin Thiersch’s skin grafts. Curr Med Pract. 1964;8:218-21.
15.Behl PN, Bhatia RK. Treatment of vitiligo with autologous thin Thiersch’s grafts. Int J Dermatol. 1973;12(5):329-31. 
16.Falabella R. Repigmentation of segmental vitiligo by autologous minigrafting. J Am Acad Dermatol. 1983;9(4):514- 21. 
17.Aziz Jalali M, Jafari B, Isfahani M, Nilforoushzadeh MA. Treatment of segmental vitiligo with normal-hair follicle autograft. Med J Islam Repub Iran. 2013;27(4):210-4. 18. Nair BK. Vitiligo--a retrospect. Int J Dermatol. 1978;17(9):755- 7. 
19.Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65(3):473-91. doi: 10.1016/j.jaad.2010.11.061. 
20.Silverberg NB. The Epidemiology of Vitiligo. Curr Dermatol Rep. 2015;4(1):36-43. doi: 10.1007/s13671-014-0098-6. 
21.Zhang Y, Cai Y, Shi M, Jiang S, Cui S, Wu Y, et al. The Prevalence of Vitiligo: A Meta-Analysis. PLoS One. 2016;11(9):e0163806. doi: 10.1371/journal.pone.0163806. 
22.Soni P, Patidar R, Soni V, Soni S. A Review on Traditional and Alteranative Treatment For Skin Disease “Vitiligo”. Int J Pharm Biol Arch. 2010;1(3):220-7. 
23.Spritz RA, Andersen GH. Genetics of Vitiligo. Dermatol Clin. 2017;35(2):245-55. doi: 10.1016/j.det.2016.11.013. 
24.Addison T. A Collection of the Published Writings of the Late Thomas Addison, M.D.: Physician to Guy’s Hospital. New Sydenham Society; 1868. 
25.Maiumder PP. Vitiligo Vulgaris. Nordlund J, ed. Vitiligo: a monograph on the basic and clinical science. WileyBlackwell; 2008:18. 
26.Alzolibani A. Genetic epidemiology and heritability of vitiligo in the Qassim region of Saudi Arabia. Acta Dermatovenerol Alp Pannonica Adriat. 2009;18(3):119-25. 
27.Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res. 2003;16(3):208-14. 
28.Majumder PP, Das SK, Li CC. A genetical model for vitiligo. Am J Hum Genet. 1988;43(2):119-25. 
29.Nath SK, Majumder PP, Nordlund JJ. Genetic epidemiology of vitiligo: multilocus recessivity cross-validated. Am J Hum Genet. 1994;55(5):981-90. 
30.Eskandani M, Hasannia S, Vandghanooni S, Pirooznia N, Golchai J. Assessment of MC1R and alpha- MSH gene sequences in iranian vitiligo patients. Indian J Dermatol. 2010;55(4):325-8. doi: 10.4103/0019-5154.74530. 
31.Czajkowski R, Mecinska-Jundzill K. Current aspects of vitiligo genetics. Postepy Dermatol Alergol. 2014;31(4):247-55. doi: 10.5114/pdia.2014.43497. 
32.Yagi H, Nomura T, Nakamura K, Yamazaki S, Kitawaki T, Hori S, et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int Immunol. 2004;16(11):1643-56. doi: 10.1093/intimm/dxh165. 
33.Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest. 2000;106(12):R75-81. doi: 10.1172/ jci11679. 
34.Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001;27(1):18-20. doi: 10.1038/83707. 
35.Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27(1):20-1. doi: 10.1038/83713. 
36.Birlea SA, Gowan K, Fain PR, Spritz RA. Genome-wide association study of generalized vitiligo in an isolated European founder population identifies SMOC2, in close proximity to IDDM8. J Invest Dermatol. 2010;130(3):798-803. doi: 10.1038/jid.2009.347. 
37.Song P, Wang XW, Li HX, Li K, Liu L, Wei C, et al. Association between FOXP3 polymorphisms and vitiligo in a Han Chinese population. Br J Dermatol. 2013;169(3):571-8. doi: 10.1111/ bjd.12377. 
38.Jahan P, Cheruvu R, Tippisetty S, Komaravalli PL, Valluri V, Ishaq M. Association of FOXP3 (rs3761548) promoter polymorphism with nondermatomal vitiligo: A study from India. J Am Acad Dermatol. 2013;69(2):262-6. doi: 10.1016/j. jaad.2013.01.035. 
39.Elela MA, Hegazy RA, Fawzy MM, Rashed LA, Rasheed H. Interleukin 17, interleukin 22 and FoxP3 expression in tissue and serum of non-segmental vitiligo: a case- controlled study on eighty-four patients. Eur J Dermatol. 2013;23(3):350-5. doi: 10.1684/ejd.2013.2023. 
40.Hegab DS, Attia MA. Decreased Circulating T Regulatory Cells in Egyptian Patients with Nonsegmental Vitiligo: Correlation with Disease Activity. Dermatol Res Pract. 2015;2015:145409. doi: 10.1155/2015/145409. 
41.Spritz RA, Gowan K, Bennett DC, Fain PR. Novel vitiligo susceptibility loci on chromosomes 7 (AIS2) and 8 (AIS3), confirmation of SLEV1 on chromosome 17, and their roles in an autoimmune diathesis. Am J Hum Genet. 2004;74(1):188- 91. doi: 10.1086/381134. 
42.Liang Y, Yang S, Zhou Y, Gui J, Ren Y, Chen J, et al. 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. 
43.Ren Y, Yang S, Xu S, Gao M, Huang W, Gao T, et al. Genetic variation of promoter sequence modulates XBP1 expression and genetic risk for vitiligo. PLoS Genet. 2009;5(6):e1000523. doi: 10.1371/journal.pgen.1000523.
44.Tarle RG, Nascimento LM, Mira MT, Castro CC. Vitiligo--part 1. An Bras Dermatol. 2014;89(3):461-70. 
45.Toosi S, Orlow SJ, Manga P. Vitiligo-inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8. J Invest Dermatol. 2012;132(11):2601-9. doi: 10.1038/jid.2012.181.
46.Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002;3(7):673-80. doi: 10.1038/ni805. 
47.Cheong KA, Chae SC, Kim YS, Kwon HB, Chung HT, Lee AY. Association of thymic stromal lymphopoietin gene -847C>T polymorphism in generalized vitiligo. Exp Dermatol. 2009;18(12):1073-5. doi: 10.1111/j.1600- 0625.2009.00897.x. 
48.Jin Y, Birlea SA, Fain PR, Gowan K, Riccardi SL, Holland PJ, et al. Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. N Engl J Med. 2010;362(18):1686-97. doi: 10.1056/NEJMoa0908547.