**9. Rheumatoid arthritis**

RA is a chronic autoimmune disorder of bone joints caused by the complex interplay between several factors like body physiology and the environment with genetic background [80, 81]. RA is characterized by synovial inflammation, hyperplasia, cartilage and bone destruction, autoantibody production (rheumatoid factor), anticyclic citrullinated peptide (CCP), and the decreased quality of life [82]. Its prevalence is approximately 0.51% worldwide and afflicts people of all races.

RA shares a number of pathogenic mechanisms with other autoimmune disorders. More than 100 loci have been associated with RA as shown in a meta-analysis of GWAS. Out of these majority (97%) are located in the noncoding region, and the remaining 3% are in various non-HLA genes including PTPN22 (Trp620Arg) [83].

Several studies have been performed on the association of PTPN22 C1858T variants with RA susceptibility in different ethnic populations (**Table 6**). Various studies have demonstrated that allelic heterogeneity distribution has an increasing north-south gradient in the frequencies of the 1858T alleles in different European populations [84]. PTPN22 C1858T polymorphism has been associated with susceptibility to RA in Algerian [85], Colombian [86, 87], Egyptian [88–90], Iranian [84, 91], Italian [92], Mexican [93–95], Spanish [96], Turkish [97], and UK Caucasian populations [65].

On the other hand, some studies reported that it is not associated with RA in Chinese [98, 99], Egyptian [100], and Iranian populations [101]. A number of meta-analyses have also shown that T-allele of PTPN22 C1858T is associated with RA susceptibility in Caucasians but not in Asians and Africans (**Table 6**) [102–104]. The different allele frequency of T-allele is very important in determining the population attributable risk of this allele for the autoimmune diseases in different populations. It also affects any suggested screening or predictive testing protocol for these diseases [101]. The absence of this association in Asians undermines the importance of this locus as a susceptibility locus for the RA and other autoimmune diseases.

## **10. Systemic lupus erythematosus**

SLE is a heterogeneous autoimmune inflammatory disease characterized by loss of self-tolerance with hyperactivation of autoreactive T and B cells with a predominance of Th2 inflammatory response [109]. The SLE incidence rate varies from 1 to 10 per 100,000 person/years, and the prevalence varies from 20 to 70 per 100,000

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

persons. SLE affects more than 300,000 people in the United States (USA) and millions worldwide [110]. It is characterized by multisystem involvement, autoantibody formation, and dysregulation of the complement system. The onset of SLE is postulated to be triggered by environmental and hormonal factors in genetically susceptible individuals [111, 112].

The genetic contribution to the development of SLE is considerably high, which is estimated to be 66% of heritability in twin studies. Genome-wide association studies (GWASs) have greatly improved our understanding of the genetic basis of SLE [113]. A high-density SNP analysis has identified and facilitated to focus on disease-associated loci where patients and healthy controls exhibit different frequencies of trait-associated alleles which are potential disease-causal variants or their proxies [113]. To date, about 100 SLE susceptibility loci have been identified, mostly in European and Asian populations [112], explaining the heritability of SLE up to around 30% [114, 115]. The highly polygenic etiology of SLE is supported by a large number of disease-associated loci that have modest effect sizes but surpass the genome-wide significance threshold for the genetic association with SLE as reviewed by Kwon et al. [112].

PTPN22 C1858T polymorphism has been associated with the pathogenesis of SLE in various populations (**Table 7**). This polymorphism is significantly associated with susceptibility to SLE in American [116–118], Columbian [86, 87], Crete [119], Spanish [96], Swedish [120], Polish [121, 122], Egyptian populations [123, 124].

Several meta-analyses also indicated that PTPN22 C1858T polymorphism is associated with SLE susceptibility [2, 107, 125–128]. On the other hand, it is not associated with SLE in Asians [118], Chinese [99, 129], Hispanics, African-Americans [118], Mexican mestizos [130], and Turkish patients [131, 132].
