A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo

Abstract

Vitiligo is an acquired hypomelanotic skin disorder resulting from the loss of functional melanocytes from the cutaneous epidermis and autoimmunity has been suggested to play a part in its pathogenesis. Recently, the missense R620W polymorphism in the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (LYP), has been associated with susceptibility to autoimmune disorders. The objective of this study was to ascertain if the disease-associated 1858T allele was also associated with generalised (nonsegmental) vitiligo and so the frequencies of the PTPN22 1858C/T alleles were investigated in 165 English patients with generalised vitiligo and 304 ethnically matched control subjects. The results indicated that the 1858T allele was significantly over-represented in the vitiligo patient group compared with the control cohort. Of 330 vitiligo alleles, 48 (14.5%) encoded the Trp620 variant compared to 52 of 608 (8.6%) control alleles (P ¼ 0.006; odds ratio ¼ 1.82, 95% confidence interval ¼ 1.17-2.82). The results indicate that the LYP missense R620W polymorphism may have an influence on the development of generalised vitiligo and provide further evidence for autoimmunity as an aetiological factor with respect to this disease.

A CD40 and an NCOA5 gene polymorphism confer susceptibility to psoriasis in a Southern European population: A case–control study

“…In this framework, it has been recently documented that a common variant of PTPN22 gene was reported to be associated with systemic lupus erythematosus (SLE) [13], rheumatoid arthritis (RA) [14], type 1 diabetes [15], juvenile idiopathic arthritis [16], systemic sclerosis [17], Wegener's granulomatosis [18], Grave's disease [19], vitiligo [20], and Addison's disease [21]. Recently, it was demonstrated that polymorphisms of CD40, a gene that is critical for innate and adaptive immunity against pathogens, located on chromosome 20q13.1, are associated with autoimmune diseases, including SLE [22], RA [23], juvenile idiopathic arthritis [24], and Grave's disease [25], thus making the genes harbored in this region attractive candidate contributors to autoimmune conditions.…”

The Non-Synonymous C1858T Substitution in the PTPN22 Gene is Associated with Susceptibility to the Severe Forms of Alopecia Areata

“…Recently, the missense R620W polymorphism in the PTPN22 gene at nucleotide 1858 (C1858T) in codon 620 (R620W) has been shown to be associated with a range of autoimmune diseases including: type 1 diabetes mellitus [10], Graves' disease [11], systemic lupus erythematosus [12], rheumatoid arthritis [12] and, more recently, vitiligo [13]. The gene, located on chromosome 1p13 [14], encodes lymphoid protein tyrosine phosphatase (LYP), which is important in the negative control of T lymphocyte activation [15].…”

Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

“…The highest T allele frequency (17.5%) was reported in northeast Russia, 14 followed by Finland (15.4%), 15 Ukraine (14.1%) 16 and Estonia (13.9%). 17 The frequency decreased toward the west, showing 11-13% in Poland, [18][19][20] 10-12% in Sweden, [21][22][23] Norway [24][25][26] and Germany, 24,[27][28][29] 11.7% in Croatia, 10-11% in the Czech Republic, 30,31 10.7% in Slovakia, 32 9.2% in Denmark, 33 and 8-10% in the UK [34][35][36][37][38][39] and the Netherlands. 24,[40][41][42] The decrease in the frequency toward the south was dramatic, with 7.75% in Hungary, 43 7.23% in Belgium, 7-8% in France, 44,45 5-7% in Spain 46-48 and 4.1% in Romania.…”

“…Both studies suggested an association between GV and PTPN22 C1858T. 34,49 Meta-analysis showed a strong association between the T allele and GV (OR ¼ 1.98; 95% CI ¼ 1.35-2.88, P ¼ 3.70 Â 10 À 04 ) ( Figure 2h). This association is supported by a recent genome-wide association studies (GWAS).…”