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

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an 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 with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA, formerly Churg-Strauss syndrome) [256].

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

**15. Myasthenia gravis**

*The Recent Topics in Genetic Polymorphisms*

risk (**Table 13**).

**16. Behcet's diseases**

determined [236, 239, 240].

with BD in Spanish patients.

**17. Endometriosis**

**98**

prevalence of the polymorphism in this population.

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

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].

BD is characterized by recurrent orogenital ulcers, cutaneous inflammation, and uveitis. It is a chronic autoimmune/inflammatory disorder with typical mucocutaneous and ocular manifestations. It also targets musculoskeletal, nervous, vascular, and gastrointestinal systems [236]. The prevalence of BD varies with geographical locations. It is more prevalent in countries along the silk route, particularly in the East Asia and the Middle East. Prevalence is highest in Turkey, followed by Egypt, Morocco, Iraq, Saudi Arabia, Japan, Iran, Korea, and China [237, 238]. Available reports indicate that autoimmunity, genetic factors, and environmental factors are involved in the pathogenesis of BD; however, the specific etiology remains to be

Being an autoimmune disease, BD is considered to be affected by PTPN22 C1858T polymorphism. However, there is no significant association of this gene in susceptibility to BD (**Table 14**). Baranathan et al. [241] suggested that PTPN22 C1858T is inversely associated with BD in the UK population indicating its protective role in BD. However, this does not hold for Middle Eastern patients in whom PTPN22 C1858T expression does not associate with BD, possibly due to a very low

The prevalence of PTPN22 C1858T is very low in the general population, and the absence of any correlation with BD indicates that PTPN22 C1858T polymorphism has a limited role in the pathogenesis of autoimmunity [242]. Recently Ortiz-Fe rnández [243] also could not find any association of PTPN22 C1858T polymorphism

Endometriosis is a chronic inflammatory disease and one of the most common benign gynecological disorders. It is a condition in which a tissue that is histologically similar to the endometrium, with glands and/or stroma, grows outside the uterine cavity [244]. It presents a multisystem involvement affecting several

with HLA polymorphisms has confirmed the central role of autoimmunity in the development of AAV. All the three main subtypes mentioned above have been reported to be associated with distinct HLA variants [258].

together with those from three other populations, showed that the 1858T allele is

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

Confounding factors must be considered particularly when polymorphisms identified in one study cannot be duplicated in a similar ethnic group. One

confounding factor is population stratification. This may occur with an unbalanced

It is clear that the inheritance of a coding variant of *PTPN22* gene is associated

The PTPN22 C1858T is one of the strongest and most consistent genetic associations with autoimmune diseases. However, available literature on PTPN22 C1858T polymorphism and autoimmune diseases shows ethnic variations. It is conceivable that the relation of any locus with the autoimmune disease will be small as interactions between gene and gene and gene and environment might also be operating. Further well-designed studies from different populations and cohorts to detect small genetic risk will help in drawing better conclusion on the development of autoimmune diseases. Therefore, further genetic studies on patients suffering from various autoimmune diseases from different ethnicities and PTPN22 gene polymorphisms are expected to help better understand the pathogenesis and will contribute

with increased susceptibility to autoimmunity. The mechanism by which the PTPN22 C1858T variant modulates disease risk has been studied. PTPN22 is capable of both enzymatic activities and adaptor functions. It exerts its effects in multiple biochemical pathways and cell types. PTPN22 regulates signaling through both antigen and innate immune receptors. It is involved in the development and activation of lymphocyte, establishment of tolerance, and innate immune cell-mediated

host defense and immunoregulation. The PTPN22 C1858T variant protein is involved in the pathogenesis of autoimmunity at multiple levels. The action of PTPN22 C1858T during immature B-cell selection disrupts the establishment of a tolerant B-cell repertoire and alters mature T-cell responsiveness. When an autoimmune attack initiates tissue injury, the TPN22C1858T fosters inflammation by

regulating the level of cytokines produced by a myeloid cell.

to the development of more targeted therapies and biomarkers.

Authors wish to thank the MSD administration for facilities and support.

associated with AAD susceptibility.

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

ethnic admixture.

**21. Conclusion**

**Acknowledgements**

**Conflict of interest**

**101**

No conflicts of interests.

The role of PTPN22 C1858T in AAV provided the basis for the three main PTPN22 genetic association studies performed so far (**Table 16**). The first, which included a German cohort, showed an association of this variant with the disease; the association was even more significant in the ANCA-positive subgroup [259]. This result has been subsequently replicated in two independent cohorts of British [260] and Italian AAV patients [261]. However, the study on Italian patients showed that the association is restricted to the GPA patients only, as almost similar frequency of the T-allele of PTPN22 C1858T was found in the MPA or the EGPA patients and controls.

Three independent meta-analyses indicated that PTPN22 C1858T polymorphism is significantly associated with susceptibility of AAV in Caucasian population [76, 262].
