**14. Systemic sclerosis**

with HT using whole-exome sequencing [157] indicating the role of *PTPN22* in autoimmune thyroid disease. However, the functional mechanism involved in the

IBD is a complex, multifactorial, chronic inflammatory disorder of the gastrointestinal tract in which immune dysregulation caused by genetic and/or environmental factors plays an important role. IBD refers to two chronic inflammatory

The IBD is a complex autoimmune disease. Its etiology is characterized by immune dysregulation caused by genetic and/or environmental factors [158, 159]. A

responses against environmental factors and/or microbes inhabiting the distal ileum and colon. It is believed that genetic factors contribute significantly to the pathogenesis of IBD [160–162]. Genome-wide scans performed in patients with IBD have failed to find a major unique susceptibility locus and have prompted the general agreement that these diseases are polygenic entities in which several genes may

Sfar et al. [163] reported an association of PTPN22 C1858T polymorphism with IBD in Tunisian patients. Recently a meta-analysis utilizing 8182 patients and 13,356 controls indicated that this is associated with CD susceptibility only and there is no association with UC [164]. No association of PTPN22 C1858T polymorphism with IBD was found in British, Canadian, Czech, German, Italian, Moroccan, New Zealander, and Spanish populations (**Table 10**). Another study on Spanish patients showed that this polymorphism is protective to CD while there is no association with UC [165]. A meta-analysis also indicated that PTPN22 C1858T polymorphism is associated with reduced susceptibility to CD with no association with UC [2]. Despite the association of PTPN22 C1858T SNP with CD and several different autoimmune disorders, a role for this polymorphism in susceptibility to IBD does

Thus, it is plausible that this genetic discrepancy in PTPN22 influences a range of diseases in which the phenotypic spectrum includes an aberrant or hyperactive immune response [5, 166]. However, these variations in the association reports of PTPN22 C1858T polymorphism with IBD may be due to ethnic variations in genetic makeup of the different populations. It has been suggested that the presence of Tallele of PTPN22 C1858T makes an individual susceptible to autoimmune diseases by helping the production of antibodies associated with these diseases, resulting in

Type 1 diabetes is an autoimmune disease in which the insulin-producing cells are attacked by the body's defense system resulting in no insulin or very little insulin production. Although the exact cause of the T1DM is not clear yet, it has been associated with both genetic and environmental factors. It usually develops in children or young adults but can affect people of all age group. The patient will die if there is no access to insulin. Therefore, daily injection of insulin is required to

The International Diabetes Federation (IDF) has reported that there were 382 million people living with diabetes worldwide in 2013 and this number is expected

genetically susceptible person develops IBD as a result of the immunogenic

association remains to be found out.

*The Recent Topics in Genetic Polymorphisms*

**12. Inflammatory bowel disease**

contribute to susceptibility [162].

the disease development [116].

**13. Type 1 diabetes mellitus**

control the blood glucose levels in patients with T1DM.

not establish.

**96**

disorders of the gastrointestinal tract: UC and CD.

SSc is a complex disease with an autoimmune origin in which extensive fibrosis, vascular alterations, and autoantibodies against various cellular antigens are among the principal features [213]. Although the etiopathogenesis is not yet well understood, the results of numerous genetic association studies support genetic contributions as an important factor to SSc.

SSc occurs in persons who are genetically predisposed and have faced specific environmental factors with or without other randomly distributed factors [214, 215]. It has been consistently associated with the major histocompatibility complex variants. Non-HLA genes associated with immunity have also been associated with SSc susceptibility [214].

In spite of these findings, the complete genetic background of SSc, the nature of its genetic determinants, and how they contribute to SSc susceptibility and clinical manifestations are poorly understood. Interestingly, PTPN22 has emerged as an important genetic risk factor for human autoimmunity. The PTPN22 C1858T polymorphism in SSc has also been investigated and shows a trend of association (**Table 12**). It has been associated with SSc susceptibility in French [216], Caucasian [214], and White, Black, and Hispanic American [217]. A meta-analysis showed that PTPN22 1858T is susceptible to SSc [107]. Some other report shows the absence of any association between this polymorphism and SSc in French [218], Columbian [87], and Spanish [219].

## **15. Myasthenia gravis**

MG is an antibody-mediated autoimmune disease against antigens at the neuromuscular junction. Both genetic and environmental factors contribute to the susceptibility of MG. The annual incidence of MG is reported to be 0.25–4 patients per 100,000 population, with the first peak of onset around the second and third decades of life and the second peak around the fifth and sixth decades [220, 221]. The exact mechanism of the autoimmunity in MG is unknown. It is caused mostly by the autoantibodies directed toward the skeletal muscle acetylcholine receptor (AChR), but there are cases in which autoimmune attack targets non-AChR components of the postsynaptic muscle endplate [222–225]. It has been suggested that genetic factors might play an important role in the development of MG [226–227]. Some studies showed that PTPN22 C1858T polymorphism is associated with MG risk (**Table 13**).

organs, most commonly in the peritoneum and pelvis, especially the ovaries, and less often in the rectovaginal septum. This results in pelvic pain, dysmenorrhea, and

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

Although various hypotheses have been proposed to explain the etiology of endometriosis, the explanation of symptoms and presence of ectopic endometrial

The etiology of endometriosis is complex and characterized by genetic and environmental factors similar to other autoimmune diseases. The immunological changes such as an increase in the number and cytotoxicity of macrophages, increase in the activity of B lymphocytes, abnormalities in the functions and concentrations of B and T lymphocytes, and reduction in the number or the activity of natural killer cells have been indicated in endometriosis. Anti-endometrial and antiovary antibodies have been also found in endometriosis [247]. As genetic factors and immunological predispositions are involved in the etiology of the disease, therefore the variants of genes associated with autoimmune diseases are possible candidates for endometriosis development [247]. PTPN22 C1858T polymorphism and its association with endometriosis have been studied in only three populations

The PTPN22 C1858T polymorphism has been reported to be associated with altered risk of endometriosis in Italian and Brazilian populations, but no significant association was found in Polish patients. However, on exploratory analyses Płoski et al. [248] suggested that the T-allele and the TT genotype may be associated with the prevalence of double positivity for antinuclear antibody (ANA) and anti-

A meta-analysis showed overall increased risk associations of up to 5.6-fold in endometriosis. In the presence of endometriosis, the PTPN22 C1858T polymorphism may cooperate with clinical and genetic factors to influence the course of disease and immune reactions. These cooperative interactions could result in a statistical association between PTPN22 C1858T and endometriosis [246].

The lymphoid tyrosine phosphatase enzyme is encoded by *PTPN22* gene and is a regulator of signaling through the T-cell receptor and forms a complex with the kinase Csk in T cells. The variant of PTPN22 C1858T polymorphism does not bind kinases properly and results in a gain-of-function enzyme [246, 249, 250]. The increased inhibition of T-cell receptor signaling caused by the PTPN22 C1858T polymorphism could predispose toward autoimmunity, either by affecting the thymic deletion of autoreactive T cells or by affecting the development or function of

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an

**18. Antineutrophil cytoplasmic antibody-associated vasculitis**

granulomatosis with polyangiitis (GPA, formerly known as Wegener's

uncommon inflammatory disease, characterized by inflammation in small- to medium-sized vessels, necrosis, and association with detectable circulating ANCAs. Though the manifestations in the lungs and kidneys are common, any organ or system can be affected. AAV refers to a group of small-vessel vasculitis, including

granulomatosis), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA,

AAV is a complex disease with both genetic and environmental factors involved in pathogenesis [257]. There is increasing evidence that susceptibility loci are shared between autoimmune diseases. The candidate gene association studies and the GWASs have shown the genetic basis of AAV. The significant association of AAV

tissue and stroma at various sites is not very clear [246].

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

(Brazilian, Italian, and Polish) so far (**Table 15**).

cardiolipin autoantibody (ACA).

peripheral regulatory T cells [251].

formerly Churg-Strauss syndrome) [256].

**99**

infertility [245].

PTPN22 C1858T polymorphism is associated with MG susceptibility in Swedish [228], German [229], European [230], Hungarian [231], and French patients [232]. However, the association between this polymorphism and the risk of MG was controversial and inconclusive in Chinese, Italian, and Turkish patients [2, 233, 234].
