Skip to main content
SpringerLink
Log in

Clinical Characteristics and PTPN22 1858C/T Variant Analysis in Jordanian Arab Vitiligo Patients

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background and Objective: Vitiligo is an autoimmune polygenic disorder, characterized by loss of pigmentation due to melanocyte destruction. Multiple genes and environmental triggers are thought to play a role in inducing vitiligo. These genes and environmental factors differ across different populations. In this study, we investigated vitiligo patients in Jordan for patient characteristics and analyzed the association of the 1858C/T (rs2476601, R620W) variant of the PTPN22 gene with vitiligo in our patients.

Methods: Fifty-five patients with generalized vitiligo and 85 matched normal control subjects who did not have vitiligo or any apparent autoimmune disorder were recruited and interviewed for clinical and demographic characteristics. DNA samples were obtained from patients and controls and genotyped by restriction fragment length polymorphism for the 1858C/T variant. Fifty-three percent of our patients (29 of 55 overall) were female, the average age at onset was 19.2 years, 84.3% of patients (43 of 51 reported) had changing size of depigmented patches, 3.8% (2 of 53 reported) had other autoimmune disease, and 19.2% (5 of 26 reported) had a family history of vitiligo.

Results: The allelic frequency of 1858T (620W) was 1.9% in patients as opposed to 2.9% in controls (p = 0.5). No PTPN22 1858 TT homozygotes were observed among patients or controls; 3.8% of vitiligo patients were 1858 CT heterozygotes compared with 5.9% of controls (p = 0.7). Consequently, no significant association was observed between the 1858C/T functional variant and vitiligo patients.

Conclusion: Although the PTPN22 1858C/T variant has been reported to play a role in increasing the risk of vitiligo in Caucasian patients, it does not appear to play a similar role in the Jordanian population, though a larger cohort of patients might be needed to confirm such a conclusion.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III

Similar content being viewed by others

References

  1. Boissy RE, Spritz RA. Frontiers and controversies in the pathobiology of vitiligo: separating the wheat from the chaff. Exp Dermatol 2009; 18(7): 583–5

    Article  PubMed  Google Scholar 

  2. Howitz J, Brodthagen H, Schwartz M, et al. Prevalence of vitiligo; epidemiological survey on the Isle of Bornholm, Denmark. Arch Dermatol 1977; 113(1): 47–52

    Article  PubMed  CAS  Google Scholar 

  3. Sun X, Xu A, Wei X, et al. Genetic epidemiology of vitiligo: a study of 815 probands and their families from South China. Int J Dermatol 2006; 45(10): 1176–81

    Article  PubMed  CAS  Google Scholar 

  4. Alkhateeb A, Fain PR, Thody A, et al. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res 2003; 16(3): 208–14

    Article  PubMed  Google Scholar 

  5. LaBerge G, Mailloux CM, Gowan K, et al. Early disease onset and increased risk of other autoimmune diseases in familial generalized vitiligo. Pigment Cell Res 2005; 18(4): 300–5

    Article  PubMed  Google Scholar 

  6. Blomhoff A, Kemp EH, Gawkrodger DJ, et al. CTLA4 polymorphisms are associated with vitiligo, in patients with concomitant autoimmune diseases. Pigment Cell Res 2005; 18(1): 55–8

    Article  PubMed  CAS  Google Scholar 

  7. Birlea SA, LaBerge GS, Procopciuc LM, et al. CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data. Pigment Cell Melanoma Res 2009; 22(2): 230–4

    Article  PubMed  Google Scholar 

  8. Retornaz G, Betuel H, Ortonne JP, et al. HL-A antigens and vitiligo. Br J Dermatol 1976; 95(2): 173–5

    Article  PubMed  CAS  Google Scholar 

  9. Le Poole IC, Luiten RM. Autoimmune etiology of generalized vitiligo. Curr Dir Autoimmun 2008; 10: 227–43

    Article  Google Scholar 

  10. Jin Y, Mailloux CM, Gowan K, et al. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 2007; 356(12): 1216–25

    Article  PubMed  CAS  Google Scholar 

  11. Jin Y, Birlea SA, Fain PR, et al. Genetic variations in NALP1 are associated with generalized vitiligo in a Romanian population. J Invest Dermatol 2007; 127(11): 2558–62

    Article  PubMed  CAS  Google Scholar 

  12. Canton I, Askhatar S, Gavalas NG, et al. A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosinase phosphatase PTPN22 confers susceptibility to generalized vitiligo. Genes Immun 2005; 6(7): 584–7

    Article  PubMed  CAS  Google Scholar 

  13. Laddha NC, Dwivedi M, Shajil EM, et al. Association of PTPN22 1858C/T polymorphism with vitiligo susceptibility in Gujarat population. J Dermatol Sci 2007; 49(3): 260–2

    Article  PubMed  Google Scholar 

  14. LaBerge GS, Bennett DC, Fain PR, et al. PTPN22 is genetically associated with risk of generalized vitiligo, but CTLA4 is not. J Invest Dermatol 2008; 128(7): 1757–62

    Article  PubMed  CAS  Google Scholar 

  15. LaBerge GS, Birlea SA, Fain PR, et al. The PTPN22-1858C>T (R620W) functional polymorphism is associated with generalized vitiligo in the Romanian population. Pigment Cell Melanoma Res 2008; 21: 206–8

    Article  PubMed  CAS  Google Scholar 

  16. Spritz RA. The genetics of generalized vitiligo. Curr Dir Autoimmun 2008; 10: 244–57

    Article  PubMed  CAS  Google Scholar 

  17. Cloutier JF, Veillette A. Cooperative inhibition of T-cell antigen receptor signaling by a complex between a kinase and a phosphatase. J Exp Med 1999; 189(1): 111–21

    Article  PubMed  CAS  Google Scholar 

  18. Bottini N, Musumeci L, Alonso A, et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004; 36

    Google Scholar 

  19. Velaga MR, Wilson V, Jennings CE, et al. The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves’ disease. J Clin Endocrinol Metab 2004; 89(11): 5862–5

    Article  PubMed  CAS  Google Scholar 

  20. Begovich AB, Carlton VE, Honigberg LA, et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 2004; 75(2): 330–7

    Article  PubMed  CAS  Google Scholar 

  21. Kyogoku C, Langefeld CD, Ortmann WA, et al. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 2004; 75(3): 504–7

    Article  PubMed  CAS  Google Scholar 

  22. Vandiedonck C, Capdevielle C, Giraud M, et al. Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis. Ann Neurol 2006; 59(2): 404–7

    Article  PubMed  CAS  Google Scholar 

  23. Skinningsrud B, Husebye ES, Gervin K, et al. Mutation screening of PTPN22: association of the 1858T-allele with Addison’s disease. Eur J Hum Genet 2008; 16(8): 977–82

    Article  PubMed  CAS  Google Scholar 

  24. Taieb A, Picardo M, VETF Members. The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force. Pigment Cell Res 2007; 20: 27–35

    Article  PubMed  Google Scholar 

  25. Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000; 132: 365–86

    PubMed  CAS  Google Scholar 

  26. Freeman GH, Halton JH. Note on exact treatment of contingency, goodness of fit and other problems of significance. Biometrika 1951; 38: 141–9

    PubMed  CAS  Google Scholar 

  27. Alzolibani A. Genetic epidemiology and heritability of vitiligo in the Qassim region of Saudi Arabia. Acta Dermatovenerol Alp Panonica Adriat 2009; 18(3): 119–25

    PubMed  Google Scholar 

  28. Arýcan O, Koç K, Ersoy L. Clinical characteristics in 113 Turkish vitiligo patients. Acta Dermatovenerol Alp Panonica Adriat 2008; 17(3): 129–32

    PubMed  Google Scholar 

  29. Criswell LA, Pfeiffer KA, Lum RF, et al. Analysis of families in the Multiple Autoimmune Disease Genetics Consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. Am J Hum Genet 2005; 76: 561–71

    Article  PubMed  CAS  Google Scholar 

  30. Arechiga AF, Habib T, He Y, et al. Cutting edge: the PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J Immunol 2009; 182(6): 3343–7

    Article  PubMed  CAS  Google Scholar 

  31. Douroudis K, Prans E, Haller K, et al. Protein tyrosine phosphatase non-receptor type 22 gene variants at position 1858 are associated with type 1 and type 2 diabetes in Estonian population. Tissue Antigens 2008; 72(5): 425–30

    Article  PubMed  CAS  Google Scholar 

  32. Korolija M, Renar IP, Hadzija M, et al. Association of PTPN22 C1858T and CTLA-4 A49G polymorphisms with type 1 diabetes in Croatians. Diabetes Res Clin Pract 2009; 86(3): e54–7

    Article  PubMed  CAS  Google Scholar 

  33. Roycroft M, Fichna M, McDonald D, et al. The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22) gene predisposes to autoimmune Addison’s disease. Clin Endocrinol (Oxf) 2009; 70(3): 358–62

    Article  CAS  Google Scholar 

  34. Steck AK, Liu SY, McFann K, et al. Association of the PTPN22/LYP gene with type 1 diabetes. Pediatr Diabetes 2006; 7(5): 274–8

    Article  PubMed  Google Scholar 

  35. Farago B, Talian GC, Komlosi K, et al. Protein tyrosine phosphatase gene C1858T allele confers risk for rheumatoid arthritis in Hungarian subjects. Rheumatol Int 2009; 29(7): 793–6

    Article  PubMed  Google Scholar 

  36. Harrison P, Pointon JJ, Farrar C, et al. Effects of PTPN22 C1858T polymorphism on susceptibility and clinical characteristics of British Caucasian rheumatoid arthritis patients. Rheumatology (Oxford) 2006; 45(8): 1009–11

    Article  PubMed  CAS  Google Scholar 

  37. Santin I, Castellanos-Rubio A, Aransay AM, et al. The functional R620W variant of the PTPN22 gene is associated with celiac disease. Tissue Antigens 2008; 71(3): 247–9

    Article  PubMed  CAS  Google Scholar 

  38. Bravo MJ, Colmenero JD, Queipo-Ortuño MI, et al. PTPN22 C1858T polymorphism and human brucellosis. Scand J Infect Dis 2009; 41(2): 109–12

    Article  PubMed  CAS  Google Scholar 

  39. Milkiewicz P, Pache I, Buwaneswaran H, et al. The PTPN22 1858T variant is not associated with primary biliary cirrhosis. Tissue Antigens 2006; 67 (5)

    Google Scholar 

  40. van Oene M, Wintle RF, Liu X, et al. Association of the lymphoid tyrosine phosphatase R620W variant with rheumatoid arthritis, but not Crohn’s disease, in Canadian populations. Arthritis Rheum 2005; 52(7): 1993–8

    Article  Google Scholar 

  41. Wesoly J, Hu X, Thabet MM, et al. The 620W allele is the PTPN22 genetic variant conferring susceptibility to RA in a Dutch population. Rheumatology (Oxford) 2007; 46(4): 617–21

    Article  CAS  Google Scholar 

  42. Dultz G, Matheis N, Dittmar M, et al. The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immune thyroiditis and autoimmune diabetes. Thyroid 2009; 19(2): 143–8

    Article  PubMed  CAS  Google Scholar 

  43. Gomez LM, Anaya JM, Gonzalez CI, et al. PTPN22 C1858T polymorphism in Colombian patients with autoimmune diseases. Genes Immun 2005; 6(7): 628–31

    Article  PubMed  CAS  Google Scholar 

  44. Lamsyah H, Rueda B, Baassi L, et al. Association of PTPN22 gene functional variants with development of pulmonary tuberculosis in Moroccan population. Tissue Antigens 2009; 74(3): 228–32

    Article  PubMed  CAS  Google Scholar 

  45. Chabchoub G, Teixiera EP, Maalej A, et al. The R620W polymorphism of the protein tyrosine phosphatase 22 gene in autoimmune thyroid diseases and rheumatoid arthritis in the Tunisian population. Ann Hum Biol 2009; 36(3): 342–9

    Article  PubMed  Google Scholar 

  46. Sahin N, Aksu K, Kamali S, et al. PTPN22 gene polymorphism in Takayasu’s arteritis. Rheumatology (Oxford) 2008; 47(5): 634–5

    Article  CAS  Google Scholar 

  47. Ray D, Tomar N, Gupta N, et al. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene R620W variant and sporadic idiopathic hypoparathyroidism in Asian Indians. Int J Immunogenet 2006; 33(4): 237–40

    Article  PubMed  CAS  Google Scholar 

  48. Zhang ZH, Chen F, Zhang XL, et al. PTPN22 allele polymorphisms in 15 Chinese populations. Int J Immunogenet 2008; 35(6): 433–7

    Article  PubMed  Google Scholar 

  49. Ichimura M, Kaku H, Fukutani T, et al. Associations of protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene polymorphisms with susceptibility to Graves’ disease in a Japanese population. Thyroid 2008; 18(6): 625–30

    Article  PubMed  CAS  Google Scholar 

  50. Baranathan V, Stanford MR, Vaughan RW, et al. The association of the PTPN22 620W polymorphism with Behcet’s disease. Ann Rheum Dis 2007; 66(11): 1531–3

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all participating patients and control subjects. We thank Dr Ziad Al-Baghdadi for his help in collecting patient samples. This work was supported by grant #43/2008 from the Deanship of Research at the Jordan University of Science and Technology. The authors have no conflicts of interest that are directly relevant to the content of this study.

Author information

Authors and Affiliations

  1. Biotechnology and Genetic Engineering Department, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan

    Asem Alkhateeb, Jude Al-Sabah & Tasnim Al Rashaideh

  2. Dermatology Department, Jordan University of Science and Technology, Irbid, Jordan

    Firas Qarqaz

Authors
  1. Asem Alkhateeb
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Firas Qarqaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jude Al-Sabah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tasnim Al Rashaideh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Asem Alkhateeb.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alkhateeb, A., Qarqaz, F., Al-Sabah, J. et al. Clinical Characteristics and PTPN22 1858C/T Variant Analysis in Jordanian Arab Vitiligo Patients. Mol Diag Ther 14, 179–184 (2010). https://doi.org/10.1007/BF03256371

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256371

Keywords

Search

Navigation