Skip to main content

Advertisement

Log in

Association of HLA alleles and haplotypes with vitiligo in Moroccan patients: a case–control study

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

The aim of this study was to identify HLA class II alleles that may be involved in vitiligo genetic susceptibility in the Moroccan population and to determine susceptible and protective HLA alleles/haplotypes in vitiligo. One-hundred unrelated vitiligo patients and 300 healthy unrelated controls were studied for HLA class II alleles by polymerase chain reaction-sequence-specific primers. The phenotypic frequency of DRB1*07 (OR = 2.23, p c = 0.014) was significantly higher, while that of DRB1*03 (OR = 0.40, p c = 0.014) was significantly lower in patients than in controls. Haplotype DRB1*07DQB1*02 (OR = 2.25, p c = 0.024) was positively associated with vitiligo patients, while haplotype DRB1*03DQB1*02 (OR = 0.35, p c = 0.012) was negatively associated with this group. Vitiligo patients with positive family history and negative anti-thyroid peroxidase antibody (anti-TPO) have an extremely high phenotype frequency of DRB1*07DQB1*02 haplotype (OR = 2.91, p c = 0.048 and OR = 2.62, p c = 0.00475, respectively). DRB1*03DQB1*02 (OR = 0.32, p c = 0.048 and OR = 0.38, p c = 0.048, respectively) was negatively associated with patients without a family history and negative anti-TPO. This study demonstrated the positive association of HLA class II alleles and haplotypes with vitiligo in the Moroccan population. There may be differences in HLA haplotypes distribution in patients according to family history and anti-TPO profile.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Al Badri AM, Foulis A, Todd PM, Gariouch JJ, Gudgeon JE, Stewart DG, Gracie JA, Goudie RB (1993) Abnormal expression of MHC class II and ICAM-1 by melanocytes in vitiligo. J Pathol 169:203–206

    Article  PubMed  CAS  Google Scholar 

  2. Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA (2003) Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res 16:208–214

    Article  PubMed  Google Scholar 

  3. Birlea SA, Ahmad FJ, Uddin RM, Ahmad S, Pal SS, Begum R, Laddha NC, Dwivedi M, Shoab Mansuri M, Jin Y, Gowan K, Riccardi SL, Holland PJ, Ben S, Fain PR, Spritz RA (2013) Association of Generalized Vitiligo with MHC Class II Loci in Patients from the Indian Subcontinent. J Invest Dermatol 133:1369–1372

    Article  PubMed  CAS  Google Scholar 

  4. Birlea SA, Gowan K, Fain PR, Spritz RA (2010) Genome-wide association study of generalized vitiligo in an isolated European founder population identifies SMOC2, in close proximity to IDDM8. J Invest Dermatol 130:798–803

    Article  PubMed  CAS  Google Scholar 

  5. Buc M, Fazekasová H, Cechová E, Hegyi E, Kolibásová K, Ferencík S (1998) Occurrence rates of HLA-DRB1, HLA-DQB1, and HLA-DPB1 alleles in patients suffering from vitiligo. Eur J Dermatol 8:13–15

    PubMed  CAS  Google Scholar 

  6. Daneshpazhooh M, Mostofizadeh GM, Behjati J, Akhyani M, Robati RM (2006) Anti-thyroid peroxidase antibody and vitiligo: a controlled study. BMC Dermatol 6:3

    Article  PubMed  Google Scholar 

  7. de Vijlder HC, Westerhof W, Schreuder GM, de Lange P, Claas FH (2004) Difference in pathogenesis between vitiligo vulgaris and halo nevi associated with vitiligo is supported by an HLA association study. Pigment Cell Res 17:270–274

    Article  PubMed  Google Scholar 

  8. Dominguez-Soto L, Hojyo-Tomoka T, Vega-Memije E, Arenas R, Cores-Franco R (1994) Pigmentary problems in the tropics. Dermatol Clin 12:777–784

    PubMed  CAS  Google Scholar 

  9. Dunston GM, Halder RM (1990) Vitiligo is associated with HLA-DR4 in black patients. Arch Dermatol 126:56–60

    Article  PubMed  CAS  Google Scholar 

  10. Excoffier L, Laval G, Schneider S (2007) Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform Online 1:47–50

    PubMed  Google Scholar 

  11. Fain PR, Babu SR, Bennett DC, Spritz RA (2006) HLA class II haplotype DRB1*04–DQB1*0301 contributes to risk of familial generalized vitiligo and early disease onset. Pigment Cell Res 19:51–57

    Article  PubMed  CAS  Google Scholar 

  12. Finco O, Cuccia M, Martinetti M, Ruberto G, Orecchia G, Rabbiosi G (1991) Age of onset in vitiligo: relationship with HLA supratypes. Clin Genet 39:48–54

    Article  PubMed  CAS  Google Scholar 

  13. Gawkrodger DJ, Ormerod AD, Shaw L, Mauri-Sole I, Whitton ME, Watts MJ, Anstey AV, Ingham J, Young K, Therapy Guidelines and Audit Subcommittee, British Association of Dermatologists, Clinical Standards Department, Royal College of Physicians of London, Cochrane Skin Group, Vitiligo Society (2008) Guideline for the diagnosis and management of vitiligo. Br J Dermatol 159:1051–1076

    Article  PubMed  CAS  Google Scholar 

  14. Gibert M, Reviron D, Mercier P, Chiaroni J, Boetsch G (2000) HLA-DRB1 and DQB1 polymorphisms in Southern France and genetic relationships with other Mediterranean populations. Hum Immunol 61:930–936

    Article  PubMed  CAS  Google Scholar 

  15. Gomez-Casado E, del Moral P, Martínez-Laso J, García-Gómez A, Allende L, Silvera-Redondo C, Longas J, González-Hevilla M, Kandil M, Zamora J, Arnaiz-Villena A (2000) HLA genes in Arabic-speaking Moroccans: close relatedness to Berbers and Iberians. Tissue Antigens 55:239–249

    Article  PubMed  CAS  Google Scholar 

  16. Grimes PE, Halder RM, Jones C, Chakrabarti SG, Enterline J, Minus HR, Kenney JA Jr (1983) Autoantibodies and their clinical significance in a black vitiligo population. Arch Dermatol 119:300–303

    Article  PubMed  CAS  Google Scholar 

  17. Hegedüs L, Heidenheim M, Gervil M, Hjalgrim H, Høier-Madsen M (1994) High frequency of thyroid dysfunction in patients with vitiligo. Acta Derm Venereol 74:120–123

    PubMed  Google Scholar 

  18. Howitz J, Brodthagen H, Schwartz M, Thomsen K (1977) Prevalence of vitiligo. Epidemiological survey on the Isle of Bornholm, Denmark. Arch Dermatol 113:47–52

    Article  PubMed  CAS  Google Scholar 

  19. Hu DY, Ren YQ, Zhu KJ, Lv YM, Cheng H, Zhang Z, Li Y, He SM, Tang J, Liu JL, Lin Y, Sun YY, Zuo XB, Chen G, Sun LD, Yang S, Zhang XJ (2011) Comparisons of clinical features of HLA-DRB1*07 positive and negative vitiligo patients in Chinese Han population. J Eur Acad Dermatol Venereol 25:1299–1303

    Article  PubMed  Google Scholar 

  20. Jin Y, Birlea SA, Fain PR, Gowan K, Riccardi SL, Holland PJ, Bennett DC, Herbstman DM, Wallace MR, McCormack WT, Kemp EH, Gawkrodger DJ, Weetman AP, Picardo M, Leone G, Taieb A, Jouary T, Ezzedine K, Geel N, Lambert J, Overbeck A, Spritz RA (2011) Genome-wide analysis identifies a quantitative trait locus in the MHC class II region associated with generalized vitiligo age of onset. J Invest Dermatol 131:1308–1312

    Article  PubMed  CAS  Google Scholar 

  21. Kemp EH (2004) Autoantibodies as diagnostic and predictive markers of vitiligo. Autoimmunity 37:287–290

    Article  PubMed  CAS  Google Scholar 

  22. Kemp EH, Wasterman EA, Weetman AP (2001) Autoimmune aspects of vitiligo. Autoimmunity 34:65–77

    Article  PubMed  CAS  Google Scholar 

  23. Kovacs SO (1998) Vitiligo. J Am Acad Dermatol 38:647–666

    Article  PubMed  CAS  Google Scholar 

  24. Laberge G, Mailloux CM, Gowan K, Holland P, Bennett DC, Fain PR, Spritz RA (2005) Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo. Pigment Cell Res 18:300–305

    Article  PubMed  Google Scholar 

  25. Le Poole IC, Das PK, Van den Wijngaard RM, Bos JD, Westerhof W (1993) Review of etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol 2:145–153

    Article  PubMed  Google Scholar 

  26. Majumder PP, Nordlund JJ, Nath SK (1993) Pattern of familial aggregation of vitiligo. Arch Dermatol 129:994–998

    Article  PubMed  CAS  Google Scholar 

  27. Mehta NR, Shah KC, Theodore C, Vyas VP, Patel AB (1973) Epidemiological study of vitiligo in Surat area, South Gujarat. Indian J Med Res 61:145–154

    PubMed  CAS  Google Scholar 

  28. Metzker A, Zamir R, Gazit E, David M, Feuerman EJ (1980) Vitiligo and the HLA system. Dermatologica 160:100–105

    Article  PubMed  CAS  Google Scholar 

  29. Quan C, Ren YQ, Xiang LH, Sun LD, Xu AE, Gao XH et al (2010) Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Nat Genet 42:614–618

    Article  PubMed  CAS  Google Scholar 

  30. Ren Y, Yang S, Xu S, Gao M, Huang W, Gao T, Fang Q, Quan C, Zhang C, Sun L, Liang Y, Han J, Wang Z, Zhang F, Zhou Y, Liu J, Zhang X (2009) Genetic variation of promoter sequence modulates XBP1 expression and genetic risk for vitiligo. PLoS Genet 5:e1000523

    Article  PubMed  Google Scholar 

  31. Roitberg-Tambur A, Witt CS, Friedmann A, Safirman C, Sherman L, Battat S, Nelken D, Brautbar C (1995) Comparative analysis of HLA polymorphism at the serologic and molecular level in Moroccan and Ashkenazi Jews. Tissue Antigens 46:104–110

    Article  PubMed  CAS  Google Scholar 

  32. Shong YK, Kim JA (1991) Vitiligo in autoimmune thyroid disease. Thyroidology 3:89–91

    PubMed  CAS  Google Scholar 

  33. Singh A, Sharma P, Kar HK, Sharma VK, Tembhre MK, Gupta S, Laddha NC, Dwivedi M, Begum R; Indian Genome Variation Consortium, Gokhale RS, Rani R (2012) HLA alleles and amino-acid signatures of the peptide-binding pockets of HLA molecules in vitiligo. J Invest Dermatol 132:124–134

    Google Scholar 

  34. Taştan HB, Akar A, Orkunoğlu FE, Arca E, Inal A (2004) Association of HLA class I antigens and HLA class II alleles with vitiligo in a Turkish population. Pigment Cell Res 17:181–184

    Article  PubMed  Google Scholar 

  35. Venkataram MN, White AG, Leeny WA, al Suwaid AR, Daar AS (1995) HLA antigens in Omani patients with vitiligo. Clin Exp Dermatol 20:35–37

    Article  PubMed  CAS  Google Scholar 

  36. Venneker GT, de Waal LP, Westerhof W, D’Amaro J, Schreuder GM, Asghar SS (1993) HLA associations in vitiligo patients in the Dutch population. Dis Markers 11:187–190

    PubMed  CAS  Google Scholar 

  37. Wang J, Zhao YM, Wang Y, Xiao Y, Wang YK, Chen HD (2007) Association of HLA class I and II alleles with generalized vitiligo in Chinese Hans in north China. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 24:221–223

    PubMed  CAS  Google Scholar 

  38. White AG, Lehny W, Kuchipudi P, Varghese M, Al Riyami H, Al Hashmi S, Daar AS (1999) Histocompatibility antigens in Omanis: comparison with other Gulf populations and implications for disease association. Ann Saudi Med 19:193–196

    PubMed  CAS  Google Scholar 

  39. Zamani M, Spaepen M, Sghar SS, Huang C, Westerhof W, Nieuweboer-Krobotova L, Cassiman JJ (2001) Linkage and association of HLA class II genes with vitiligo in a Dutch population. Br J Dermatol 145:90–94

    Article  PubMed  CAS  Google Scholar 

  40. Zhang XJ, Liu HS, Liang YH, Sun LD, Wang JY, Yang S, Liu JB, Gao M, He PP, Cui Y, Yang Q (2004) Association of HLA class I alleles with vitiligo in Chinese Hans. J Dermatol Sci 35:165–168

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are indebted to our colleagues Dr. Jihane koufane and Dr. Yassmine ouidane (Department of dermatology, Ibn Sina hospital Rabat) for their fruitful contributions, and to Pr. Samir Ahid (Department of biostatistics, Faculty of medicine and pharmacy of Rabat) for his assistance. We are most grateful to all the patients who participated in this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Abdellatif Bouayad.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bouayad, A., Benzekri, L., Hamada, S. et al. Association of HLA alleles and haplotypes with vitiligo in Moroccan patients: a case–control study. Arch Dermatol Res 305, 925–932 (2013). https://doi.org/10.1007/s00403-013-1368-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-013-1368-z

Keywords

Navigation