Polymorphisms in the Melanocortin-1 Receptor (Mc1R) Gene in Vitiligo

Abstract

Objective: Vitiligo is a progressive skin pigmentation disorder, which may be acquired or hereditary, frequently seen, and may influence every age group. The melanocortin 1 receptor (MC1R) gene is a major determinant of human pigmentation. In our study, polymorphic differences of the MC1R gene at the DNA level has been investigated in patients with vitiligo. Materials and Methods: In our study, polymorphic differences of the MC1R gene at the DNA level has been investigated in vitiligo 60 patients, whose families had resided in the Thrace region of Turkey for at least three generations. The 60 volunteer healthy individuals have no other systemic and dermatological disease. Results: Totally, five types of Single Nucleotide Polymorphism (SNP) were found in each case and control groups: Val60Leu (G178T), Val92Met (G274A), Arg151Cys (C451T), Arg160Trp (C478T), and Arg163Gln (G488A). Comparing both groups in terms of genotype frequencies, no statistically meaningful difference was detected (p>0.05). However, assessing in terms of allele frequencies, a meaningful difference was found in the Arg163Gln (G488A) allele statistically in favor of the control group (p<0.05). Conclusion: It has been found in our study population that the MC1R gene Arg163Gln (G488A) allele may be a protective factor for vitiligo. Turkish Başlık: Vitiligoda Melanokortin-1 Reseptör Geni Polimorfizmleri Anahtar Kelimeler: Vitiligo, Melanokortin-1 Reseptör Geni, Polimorfizm Amaç: Vitiligo; her yaş grubunda, herediter veya kazanılmış olarak ve sıklıkla görülen, ilerleyici, bir deri pigmentasyon bozukluğudur. Melanokortin 1 reseptör (MC1R) geni insan pigmentasyonunda major bir belirleyicidir. Bizim çalışmamızda; vitiligolu olgularda MC1R genindeki polimorfik farklılıklar DNA seviyesinde araştırılmaktadır. Hastalar ve Yöntemler: Bizim çalışmamızda; MC1R genindeki polimorfik farklılıklar en az üç kuşaktır Türkiye'nin Trakya bölgesinde yaşayan, başka bir diğer sistemik veya dermatolojik bir hastalığı olmayan, 60 vitiligolu olguda ve 60 gönüllü sağlıklı bireyde DNA seviyesinde araştırılmıştır. Bulgular: Kontrol ve olgu gruplarının her birisinde toplam 5 adet SNP bulunmuştur. Val60Leu (G178T), Val92Met (G274A), Arg151Cys (C451T), Arg160Trp (C478T) and Arg163Gln (G488A). Genotip sıklıkları yoluyla her iki grup karşılaştırıldığında istatistiki olarak anlamlı bir fark bulunmadı (p>0.05). Ancak allel sıklıkları yoluyla değerlendirildiğinde kontrol grubunun lehine Arg163Gln (G488A) allelinde istatistiki olarak anlamlı bir fark bulundu(p<0.05). Sonuç: Bundan dolayı, bizim çalışmamıza göre MC1R geni Arg163Gln (G488A) alleli vitiligo için koruyucu bir faktör olabilir.

Keywords

• Vitiligo, MC1R, melanocortin-1 receptor gene, polymorphism

Polymorphisms in the Melanocortin-1 Receptor (Mc1R) Gene in Vitiligo

Öz

References

1. Mosher DB, Fitzpatrick TB, Ortonne JP, Hori Y. Hypomelanoses and hypermelanoses. In: Freed IM, Eisen AZ, Wolf K, Austen KF, Goldsmith LA, Katz SI et al, editors. Dermatology in general medicine. 5th ed. New York: Mc Graw Hill Co; 1999. p. 945-1017.
2. Denli G, Acar MA, Maraklı SS, Yücel A. Vitiligo. In: Tuzun Y, Gurer MA, Serdaroğlu S, Oguz O, Aksungur VL editors. Dermatoloji. 3rd ed. Istanbul: Nobel Tıp Kitabevi; 2008. p. 1465-90.
3. Kovacs SO. Vitiligo. J Am Acad Dermatol 1998;38:647-66. [CrossRef]
4. Sturm RA, Teasdale RD, Box NF. Human pigmentation genes: identification, structure and consequences of polymorphic varia- tion. Gene 2001;277:49-62. [CrossRef]
5. Rees JL. Genetics of hair and skin color. Annu Rev Genet 2003;37:67-90. [CrossRef]
6. Schaffer JV, Bolognia JL. The melanocortin-1 receptor red hair and beyond. Arch Dermatol 2001;137:1477-85.
7. Cone RD, Mountjoy KG, Robbins LS, Nadeau JH, Johnson KR, Roselli- Rehfuss L, et al. Cloning and functional characterization of a family of receptors for the melanotropic peptides. Ann NY Acad Sci 1993;680:342-63. [CrossRef]
8. Falco OB, Plewig G, Wolff HH, Burgdorf WHC, (editors). Derma- tology. Berlin: Springer-Verlag; 2001.

9. Bystryn JC. Immune mechanisms in vitiligo. Clin Dermatol 1997;15:853-61. [CrossRef]
10. van den Wijngaard RM, Aten J, Scheepmaker A, Le Poole IC, Tigges AJ, Westerhof W, et al. Expression and modulation of apoptosis regulatory molecules in human melanocytes: signifi- cance in vitiligo. Br J Dermatol 2000;143:573-81. [CrossRef]
11. Nordlund JJ. The epidemiology and genetics of vitiligo. Clin Der- matol 1997;15:875-8. [CrossRef]
12. De Vijlder HC, Westerhof W, Schreuder GM, de Lange P, Claas FH. Difference in pathogenesis between vitiligo vulgaris and halo nevi associated with vitiligo is supported by an HLA assocition study. Pigm Cell Res 2004;17:270-4. [CrossRef]
13. al-Fouzan A, al-Arbash M, Fouad F, Kaaba SA, Mousa MA, al-Har- bi SA. Study of HLA class I/IL and T lymphocyte subsets in Kuwaiti vitiligo patients. Eur J Immunogenet 1995;22:209-13. [CrossRef]
14. Orecchia G, Perfetti L, Malagoli P, Borghini F, Kipervag Y. Vitiligo is associated with a significant increase in HLA-A30, Cw6 and DQw3 and a decrease in C4AQ0 in northern Italian patients. Der- matology 1992;185:123-7. [CrossRef]
15. Zamani M, Spaepen M, Sghar SS, Huang C, Westerhof W, Nieuweboer-Krobotova L, et al. Linkage and association of HLA class II genes with vitiligo in a Dutch population. Br J Dermatol 2001;145:90-4. [CrossRef]
16. Szell M, Baltas E, Bodai L, Bata-Csorgo Z, Nagy N, Dallos A, et al. The Arg160Trp Allele of Melanocortin-1 Receptor Gene Might Protect Against Vitiligo. Photochem Photobiol 2008;84:565-71. [CrossRef]
17. Na GY, Lee KH, Kim MK, Lee SJ, Kim DW, Kim JC. Polymorphisms in the melanocortin-1 receptor (MC1R) and agouti signaling pro- tein (ASIP) genes in Korean vitiligo patients. Pigment Cell Res 2003;16:383-7. [CrossRef]
18. Başaran N. (editor). Tıbbi genetik ders kitabı. Istanbul: Nobel Tıp Kitabevi; 2003.
19. Steiner D, Bedin V, Moreas MB, Villas RT, Steiner T. Vitiligo. An Bras Dermatol 2004;79:335-51. [CrossRef]
20. Ongenae K, Geel NV, Naeyaert JM. Evidence for an autoim- mune pathogenesis of vitiligo. Pigment Cell Res 2003;16:90-100. [CrossRef]
21. Jimbow K, Quevedo WC, Prota G, Fitzpatrick TB. Biology of me- lanocytes. In: Freed IM, Eisen AZ Wolf K, Austen KF, Goldsmith LA, Katz SI et al. editors. Dermatology in general medicine. 5th ed. New York: Mc Graw Hill Co; 1999. p. 192-220.
22. Waterman EA, Kemp EH, Gawkrodger DJ, Watson PF, Weetman AP. Autoantibodies in vitiligo patients are not directed to the melanocyte differentiation antigen MelanA/MART1. Clin Exp Im- munol 2002;129:527-32. [CrossRef]
23. Rocha IM, Oliveira LJN, Castro LCM, Pereira LIA, Chaul A, Guerra JG, et al. Recognition of melanoma cell antigens with antibod- ies present in sera from patients with vitiligo. Int J Dermatol 2000;39:840-3. [CrossRef]