Skip to main content
Top
Published in: Archives of Dermatological Research 10/2013

01-12-2013 | Original Paper

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

Authors: Abdellatif Bouayad, L. Benzekri, S. Hamada, C. Brick, B. Hassam, M. Essakalli

Published in: Archives of Dermatological Research | Issue 10/2013

Login to get access

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.
Literature
1.
go back to reference 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 169:203–206PubMedCrossRef 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 169:203–206PubMedCrossRef
2.
go back to reference 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 16:208–214PubMedCrossRef 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 16:208–214PubMedCrossRef
3.
go back to reference 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 133:1369–1372PubMedCrossRef 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 133:1369–1372PubMedCrossRef
4.
go back to reference 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 130:798–803PubMedCrossRef 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 130:798–803PubMedCrossRef
5.
go back to reference 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 8:13–15PubMed 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 8:13–15PubMed
6.
go back to reference Daneshpazhooh M, Mostofizadeh GM, Behjati J, Akhyani M, Robati RM (2006) Anti-thyroid peroxidase antibody and vitiligo: a controlled study. BMC Dermatol 6:3PubMedCrossRef Daneshpazhooh M, Mostofizadeh GM, Behjati J, Akhyani M, Robati RM (2006) Anti-thyroid peroxidase antibody and vitiligo: a controlled study. BMC Dermatol 6:3PubMedCrossRef
7.
go back to reference 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 17:270–274PubMedCrossRef 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 17:270–274PubMedCrossRef
8.
go back to reference Dominguez-Soto L, Hojyo-Tomoka T, Vega-Memije E, Arenas R, Cores-Franco R (1994) Pigmentary problems in the tropics. Dermatol Clin 12:777–784PubMed Dominguez-Soto L, Hojyo-Tomoka T, Vega-Memije E, Arenas R, Cores-Franco R (1994) Pigmentary problems in the tropics. Dermatol Clin 12:777–784PubMed
9.
go back to reference Dunston GM, Halder RM (1990) Vitiligo is associated with HLA-DR4 in black patients. Arch Dermatol 126:56–60PubMedCrossRef Dunston GM, Halder RM (1990) Vitiligo is associated with HLA-DR4 in black patients. Arch Dermatol 126:56–60PubMedCrossRef
10.
go back to reference Excoffier L, Laval G, Schneider S (2007) Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform Online 1:47–50PubMed Excoffier L, Laval G, Schneider S (2007) Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evol Bioinform Online 1:47–50PubMed
11.
go back to reference 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 19:51–57PubMedCrossRef 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 19:51–57PubMedCrossRef
12.
go back to reference Finco O, Cuccia M, Martinetti M, Ruberto G, Orecchia G, Rabbiosi G (1991) Age of onset in vitiligo: relationship with HLA supratypes. Clin Genet 39:48–54PubMedCrossRef Finco O, Cuccia M, Martinetti M, Ruberto G, Orecchia G, Rabbiosi G (1991) Age of onset in vitiligo: relationship with HLA supratypes. Clin Genet 39:48–54PubMedCrossRef
13.
go back to reference 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 159:1051–1076PubMedCrossRef 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 159:1051–1076PubMedCrossRef
14.
go back to reference 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 61:930–936PubMedCrossRef 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 61:930–936PubMedCrossRef
15.
go back to reference 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 55:239–249PubMedCrossRef 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 55:239–249PubMedCrossRef
16.
go back to reference 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 119:300–303PubMedCrossRef 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 119:300–303PubMedCrossRef
17.
go back to reference Hegedüs L, Heidenheim M, Gervil M, Hjalgrim H, Høier-Madsen M (1994) High frequency of thyroid dysfunction in patients with vitiligo. Acta Derm Venereol 74:120–123PubMed Hegedüs L, Heidenheim M, Gervil M, Hjalgrim H, Høier-Madsen M (1994) High frequency of thyroid dysfunction in patients with vitiligo. Acta Derm Venereol 74:120–123PubMed
18.
go back to reference Howitz J, Brodthagen H, Schwartz M, Thomsen K (1977) Prevalence of vitiligo. Epidemiological survey on the Isle of Bornholm, Denmark. Arch Dermatol 113:47–52PubMedCrossRef Howitz J, Brodthagen H, Schwartz M, Thomsen K (1977) Prevalence of vitiligo. Epidemiological survey on the Isle of Bornholm, Denmark. Arch Dermatol 113:47–52PubMedCrossRef
19.
go back to reference 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 25:1299–1303PubMedCrossRef 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 25:1299–1303PubMedCrossRef
20.
go back to reference 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 131:1308–1312PubMedCrossRef 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 131:1308–1312PubMedCrossRef
21.
go back to reference Kemp EH (2004) Autoantibodies as diagnostic and predictive markers of vitiligo. Autoimmunity 37:287–290PubMedCrossRef Kemp EH (2004) Autoantibodies as diagnostic and predictive markers of vitiligo. Autoimmunity 37:287–290PubMedCrossRef
22.
24.
go back to reference 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 18:300–305PubMedCrossRef 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 18:300–305PubMedCrossRef
25.
go back to reference Le Poole IC, Das PK, Van den Wijngaard RM, Bos JD, Westerhof W (1993) Review of etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol 2:145–153PubMedCrossRef Le Poole IC, Das PK, Van den Wijngaard RM, Bos JD, Westerhof W (1993) Review of etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol 2:145–153PubMedCrossRef
26.
go back to reference Majumder PP, Nordlund JJ, Nath SK (1993) Pattern of familial aggregation of vitiligo. Arch Dermatol 129:994–998PubMedCrossRef Majumder PP, Nordlund JJ, Nath SK (1993) Pattern of familial aggregation of vitiligo. Arch Dermatol 129:994–998PubMedCrossRef
27.
go back to reference Mehta NR, Shah KC, Theodore C, Vyas VP, Patel AB (1973) Epidemiological study of vitiligo in Surat area, South Gujarat. Indian J Med Res 61:145–154PubMed Mehta NR, Shah KC, Theodore C, Vyas VP, Patel AB (1973) Epidemiological study of vitiligo in Surat area, South Gujarat. Indian J Med Res 61:145–154PubMed
28.
go back to reference Metzker A, Zamir R, Gazit E, David M, Feuerman EJ (1980) Vitiligo and the HLA system. Dermatologica 160:100–105PubMedCrossRef Metzker A, Zamir R, Gazit E, David M, Feuerman EJ (1980) Vitiligo and the HLA system. Dermatologica 160:100–105PubMedCrossRef
29.
go back to reference 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 42:614–618PubMedCrossRef 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 42:614–618PubMedCrossRef
30.
go back to reference 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:e1000523PubMedCrossRef 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:e1000523PubMedCrossRef
31.
go back to reference 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 46:104–110PubMedCrossRef 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 46:104–110PubMedCrossRef
32.
go back to reference Shong YK, Kim JA (1991) Vitiligo in autoimmune thyroid disease. Thyroidology 3:89–91PubMed Shong YK, Kim JA (1991) Vitiligo in autoimmune thyroid disease. Thyroidology 3:89–91PubMed
33.
go back to reference 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 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
34.
go back to reference 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 17:181–184PubMedCrossRef 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 17:181–184PubMedCrossRef
35.
go back to reference Venkataram MN, White AG, Leeny WA, al Suwaid AR, Daar AS (1995) HLA antigens in Omani patients with vitiligo. Clin Exp Dermatol 20:35–37PubMedCrossRef Venkataram MN, White AG, Leeny WA, al Suwaid AR, Daar AS (1995) HLA antigens in Omani patients with vitiligo. Clin Exp Dermatol 20:35–37PubMedCrossRef
36.
go back to reference 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 11:187–190PubMed 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 11:187–190PubMed
37.
go back to reference 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 24:221–223PubMed 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 24:221–223PubMed
38.
go back to reference 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 19:193–196PubMed 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 19:193–196PubMed
39.
go back to reference 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 145:90–94PubMedCrossRef 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 145:90–94PubMedCrossRef
40.
go back to reference 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 35:165–168PubMedCrossRef 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 35:165–168PubMedCrossRef
Metadata
Title
Association of HLA alleles and haplotypes with vitiligo in Moroccan patients: a case–control study
Authors
Abdellatif Bouayad
L. Benzekri
S. Hamada
C. Brick
B. Hassam
M. Essakalli
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 10/2013
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-013-1368-z

Other articles of this Issue 10/2013

Archives of Dermatological Research 10/2013 Go to the issue