**12. Inflammatory bowel disease**

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 disorders of the gastrointestinal tract: UC and CD.

The IBD is a complex autoimmune disease. Its etiology is characterized by immune dysregulation caused by genetic and/or environmental factors [158, 159]. A genetically susceptible person develops IBD as a result of the immunogenic 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 contribute to susceptibility [162].

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 not establish.

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 the disease development [116].

## **13. Type 1 diabetes mellitus**

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 control the blood glucose levels in patients with T1DM.

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

### *The Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Gene Polymorphism… DOI: http://dx.doi.org/10.5772/intechopen.90836*

to rise to 592 million by 2035 [176]. Most people with diabetes live in low- and middle-income countries, where rapid changes in lifestyle have increased the prevalence of diabetes, cardiovascular diseases, and cancer, and these countries are expected to experience the greatest increase in cases of diabetes in the next 20 years. The global prevalence of diabetes was reported as 8.8% of the world's population (95% confidence interval 7.2–11.3%) in 2017, and it is expected to increase to 9.9% in 2045 [177]. At present in every seventh second, someone dies from diabetes or its complications. Fifty percent of these deaths are under the age of 60 years.

According to a report, 424.9 million people were having diabetes worldwide in 2017 which is expected to increase to 628.6 million people in 2045. The prevalence of diabetes is continuously increasing since the IDF Diabetes Atlas first was launched in 2000, and about 50% of the diabetes cases remain undiagnosed especially in developing countries which is a matter of concern [177].

A positive association between PTPN22 C1858 T polymorphism and susceptibility to the development of T1DM has been reported in a large number of studies from several populations (**Table 11**) with the exception of a few such as a single study from Chinese [178], Greek [179], Indian [180], and Iranian populations [181] where no association was found.

The review by Prezioso et al. [182] evaluated the role of the PTPN22 C1858 T in the prognosis of disease. On the basis of the potential role of C1858 T as a target for tertiary prevention trials and new therapeutic strategies, such as the Lyp inhibitors, they suggested that PTPN22 can be a promising target for therapeutic interventions and identification of at-risk subjects in autoimmune diseases such as T1DM.

It has been shown that several SNPs could potentially contribute to susceptibility to various autoimmune disorders including T1DM. However, 1858C/T SNP is the most stable, where T-allele correlates with T1DM (**Table 11**) [7, 142, 152, 183]. Habib et al. [211] demonstrate a role of PTPN22 1858T in signaling defects in both transitional and naïve B cells in healthy subjects resulting in an increased resistance to BCRdriven apoptosis in these cells and peripheral reservoir of autoreactive cells [212].
