**1. Introduction**

Genetic polymorphisms are variations in DNA found in 1% or more of the population which may alter the structure and function of protein through a single nucleotide base substitution in a gene's coding region. It may alter the gene expression either by affecting mRNA stability when occurring in a gene's 3<sup>0</sup> -untranslated region or by changing transcription factor binding when occurring in the 5<sup>0</sup> -promoter region. A polymorphism does not have any effect on the protein product when it occurs within DNA regions that are not involved in gene transcription or translation but serves as the basis for genetic linkage analysis [1].

The information on genetic polymorphisms facilitates to explain pathologic mechanisms and help in identifying individuals at risk. It also helps us to find novel targets for drug treatment. The protein tyrosine phosphatase non-receptor type 22 (*PTPN22*) gene is an important predisposing gene for human autoimmune diseases. The alterations in PTPN22 render a person susceptible and lead to the development of several autoimmune diseases. Many single nucleotide polymorphisms (SNPs) have been identified in PTPN22, but only one non-synonymous SNP has been intensively studied in relation to autoimmune diseases. This SNP C1858T (rs2476601) in exon 14 of the PTPN22 gene has been associated with a number of autoimmune diseases and considered as a risk factor due to significant production of autoantibodies [2, 3].

studies. Therefore, the focus should be on the way genetic associations are reported. Even in the overlapping meta-analyses on the same topic, the limitations such as inclusion and exclusion criteria and number of included studies result in consistency of association results of genes, although the meta-analysis has been considered as a powerful approach to identify true-positive association of genes with

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

The PTPN22 C1858T variant has been studied in several autoimmune or autoimmunity-related diseases in different ethnic populations worldwide.

Autoimmune diseases are pathological conditions identified by abnormal autoimmune responses and characterized by autoantibodies and T-cell responses to self-molecules by immune system reactivity. Human autoimmune diseases occur frequently (affecting in aggregate more than 5% of the population worldwide) and impose a significant burden of morbidity and mortality on the human

The etiology of autoimmune diseases involves both genetic and environmental factors. Familial clustering is known in autoimmune diseases with higher rate of concordance in monozygotic twins as compared to dizygotic twins [10–12]. Most autoimmune diseases are multigenic, with multiple susceptibility genes working in concert to produce the disease; however, a few autoimmune diseases are caused by mutations in a single gene. Even in such cases other genes modify the severity of disease. On the other hand, some individuals with these mutations do not manifest

The genetic polymorphisms also occur in normal population and are compatible with a normal immune function. However, when these polymorphisms occur with

**Population Case/controls Genotype/allele/polymorphism Association References** Mexican 187/223 CT Susceptible [20] Indian (Tamils) 264/264 CT Susceptible [25] Indian (Gujarati) 126/140 C1858T No association [32] English 165/304 C1858T Susceptible [29] Romanian – T-allele Susceptible [30]

T-allele

T-allele

1514/2813 C1858T Susceptible [31]

Turkish 107/112 C1858T No association [27]

Jordanian 55/85 C1858T No association [33] Egyptian 100/120 C1858T No association [34]

Susceptible No association

Susceptible No association [28]

[26]

2094/3613 T-allele

1800/3269 T-allele

*Association of PTPN22 C1858T polymorphism with* vitiligo *susceptibility.*

disease.

**3. Autoimmune diseases**

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

population [9].

the disease.

European\* Asian

European\* Asian

Caucasian# European

*Meta-analysis.*

*Genome-wide association study.*

*\**

*#*

**83**

**Table 1.**

The PTPN22 C1858T variant has been studied in autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus, juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, vitiligo, systemic sclerosis (SSc), Graves' disease (GD), myasthenia gravis (MG), Addison's disease, psoriasis, psoriatic arthritis (PsA), Behcet's disease (BD), endometriosis, autoimmune thyroid disease (AITD), giant cell arteritis (GCA), alopecia areata (AA), and Sjögren's syndrome. The association of PTPN22 C1858T genetic polymorphism is very significant and noteworthy in some autoimmune diseases, while in other it is less significant [3]. However, available literature on PTPN22 C1858T polymorphism and autoimmune diseases shows inconsistencies and ethnic variations exist.
