**4. Vitiligo**

Vitiligo is an acquired, autoimmune skin disorder characterized by melanocyte loss resulting into progressive depigmentation of the skin and hair [15, 16]. The prevalence of vitiligo varies considerably with ethnicity and it affects 0.1–2% of the population worldwide [15, 17]. Vitiligo is associated with an elevated risk of several other autoimmune diseases [18–20].

Vitiligo commonly shows familial aggregation and multifactorial mode of inheritance. It is a polygenic disease, and several genes related to autoimmunity have been reported to be associated with the pathogenesis of vitiligo [20–25].

Various published reports on PTPN22 C1858T polymorphism support the association of the T-allele and vitiligo susceptibility in different ethnic populations (**Table 1**). However, available literature on the PTPN22 C1858T polymorphism and vitiligo susceptibility is inconsistent [25–28]. It has been reported to be a risk factor for vitiligo in English, Romanian, North American, Mexican, and South Indian Tamil populations [20, 25, 29, 30]. PTPN22 C1858T polymorphism is strongly associated with vitiligo susceptibility in Saudis also [in press]. A genome-wide association study indicates that PTPN22 C1858T is associated with vitiligo in European-derived white patients [Jin et al. 2010]. A meta-analysis utilizing data from different ethnicities shows an association of PTPN22 C1858T with vitiligo in European but not in Asian population [28].

Though the pathogenesis of psoriasis and comorbidities has been studied at the molecular level and a number of gene loci have been associated with susceptibility/ severity of psoriasis [50–53], genes identified till date to be associated with it do not fully account for it. Psoriasis is highly heritable, and it has been suggested in several association studies that skin barrier function, innate and adaptive immunity, and gene-gene and gene-environment interactions are involved in the pathogenesis of

*The Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Gene Polymorphism…*

Recently an association of T-allele of the PTPN22 C1858T with susceptibility to

psoriasis in Saudi population was reported (**Table 3**) [53]. Earlier it has been suggested that *PTPN22* may be among the true psoriasis susceptibility risk genes [54]. However, another study analyzed 15 SNPs from 7 putative psoriasis-risk genes and could not find any significant association of PTPN22 C1858T polymorphism with psoriasis. On the other hand, they found a significant association with another polymorphism (rs3789604) in *PTPN22* gene and suggested that *PTPN22* is one of the significant risk genes for psoriasis [55]. Chen and Chang [56] reported a strong association of PTPN22 + 1858T allele with PsA but no association with psoriasis and

suggested that attention should be given to the studies dealing with gene-

of the disease and population stratification.

*DOI: http://dx.doi.org/10.5772/intechopen.90836*

tibility in German psoriasis patients.

in the pathogenic process of PsA.

**8. Juvenile idiopathic arthritis**

**93**

T-allele than in the subgroup of female patients [66].

**7. Psoriatic arthritis**

environment interaction besides keeping in consideration the clinical heterogeneity

(+1858T allele) with psoriasis and suggested that other susceptibility locus/loci within noncoding regions of *PTPN22* or its proximity might exist and act independently as a risk factor. They excluded the direct link of T-allele in psoriasis suscep-

Earlier Hüffmeier et al. [57] found gender variations in susceptibility of PTPN22

PsA is a chronic inflammatory arthritis associated with psoriasis. PsA is a chronic skin and joint condition that considerably affects patient's quality of life. PsA is a complex disease with environmental and genetic risk factors contributing to it. Several studies have demonstrated different associations of genetic polymorphisms

PTPN22 C1858T polymorphism has also been strongly associated with PsA (**Table 4**) in Toronto admix and Swedish population [61, 62]. Several non-HLA loci including *PTPN22* have been suggested to affect the susceptibility to PsA [63, 64]. A complete genetic overlap has been suggested between psoriasis and PsA susceptibility loci as about a third of people who have psoriasis gets PsA. It has been noticed that subjects with severe psoriasis have a greater chance of getting PsA and about 40% of patients with PsA have relatives with it or with psoriasis, while other earlier studies reported no association of PTPN22 C1858T polymorphism and PsA in Newfoundland, the UK, and German Caucasian [57, 61, 65]. Though no significant differences were observed in allele distribution with different manifestations of disease, there is gender difference, and male PsA patients has higher frequency of

JIA is the most common inflammatory disease of the joints in children. Its etiology is complex and involves both genetic and environmental factors. It has been suggested that genetic factors play a significant role in the susceptibility to JIA [67]. While associations between JIA and variants in HLA are well established,

psoriasis [52].

In contrast, no significant association of PTPN22 C1858T polymorphism with susceptibility to generalized vitiligo was found in Indian Gujarat population, Jordanian, Egyptian female, and Turkish population [27, 32–34]. Available literature shows that the variant of PTPN22 C1858T is responsible for increased risk of vitiligo in Caucasian patients; however, among non-Caucasians/Asians, inconsistency exits, and even the two populations of same country differ in association of PTPN22 C1858T with vitiligo indicating the role of ethnicity. The heterozygous CT genotype of the PTPN22 C1858T has a strong association with non-segmental vitiligo in South Indian Tamils, while there is no association of this polymorphism in Indian Gujarat population [25, 32]. This difference in the results of this polymorphism in Asians or non-Caucasians can be attributed to ethnic differences.

## **5. Alopecia areata (AA)**

AA is a dermatological condition in which hair is lost from certain or all areas of the body, typically from certain areas of the scalp, more frequent in young ones [35]. The characteristic feature of AA is circular or oval bald spots which may progress and spread to the entire scalp (alopecia totalis) or entire body (alopecia universalis). Sometimes hair loss is localized to the sides and lower back of the scalp which is known as alopecia ophiasis [36]. The prevalence of AA in the general population varies between 0.1 and 6.9% depending on the ethnic group [37].

Alopecia areata is an autoimmune disease mediated by T cells to the hair follicles. There are enough evidences indicating that AA is a complex multigenetic trait with components of inherited predisposition. Molecular biology studies have led to the identification of a number of candidate genes in humans that confer susceptibility to AA. Recently, PTPN22 gene has been reported to be an additional immunoregulatory gene associated with AA. PTPN22 C1858T polymorphism has been associated with susceptibility of AA in Belgian, English, Egyptian, German, and Mexican populations (**Table 2**) [38–43]. Two meta-analyses have also indicated an association with AA susceptibility [42, 43]. However, no association of PTPN22 C1858T has been found in Iranian patients [44].
