**8. Juvenile idiopathic arthritis**

JIA is the most common inflammatory disease of the joints in children. Its etiology is complex and involves both genetic and environmental factors. It has been suggested that genetic factors play a significant role in the susceptibility to JIA [67]. While associations between JIA and variants in HLA are well established,

non-HLA genetic variants also play a role in JIA susceptibility and have increasingly been identified by genome-wide and candidate gene studies [68, 69]. Many of the genetic associations have been confirmed recently by the International JIA Immunochip consortium, and several novel loci have also been identified showing a genome-wide association.

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

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

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

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].

Autoimmune thyroid disease (AITD) is a complex disease which includes GD and Hashimoto's thyroiditis (HT). Its susceptibility is influenced by both genetic and environmental factors. The interaction of specific susceptibility genes and environmental exposures have been associated with AITD [135]. Both GD and HT are characterized by the production of thyroid autoantibodies and the invasion of thyroid lymphocytes. AITD is found in 5% of the general population and is one of the most prevalent autoimmune diseases. The incidence of GD and HT is influenced by genetic factors as well as environmental factors including geographical locations [136]. Approximately 37% of families with AITD exhibit either of these two

Previous molecular studies on genetic etiology of AITD have expanded the field

PTPN22 C1858T polymorphism has been associated with GD (**Table 9**). It is susceptible to GD in Latin-American [148], Polish [149, 150], and English Caucasian populations [140, 151, 152]. Two separate meta-analyses confirmed the association of PTPN22 + 1858C/T polymorphism with Graves' disease [2, 139]. However, some reports have indicated no correlation between PTPN22 + 1858C/T and Graves'

disease in Chinese Han, Polish, and Indian Kashmiri populations [153–155]. Jacobson et al. [156] reported that the PTPN22 + 1858C/T is related to the occurrence of HT. Another variant in PTPN22 gene has been found to be associated

of thyroid autoimmunity. Previous studies have shown that PTPT22 C1858T is associated with AITD [138, 139] (**Table 8**). Some reports have indicated a positive correlation [140–142], while others have indicated no correlation between PTPN22 C1858T and AITD in Japanese [143, 144], Korean [145], Jordanian, [146], and

The genetic contribution to the development of SLE is considerably high, which

susceptible individuals [111, 112].

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

reviewed by Kwon et al. [112].

**11. Autoimmune thyroid disease**

disorders [137].

**95**

Polish populations [147].

Several reports indicate that PTPN22 C1858T polymorphism has been consistently associated with JIA (**Table 5**). PTPN22 C1858T polymorphism is associated with JIA in Australians [70, 71], Americans of European ancestry [67], Czech [72], Europeans [69], Greek [73], Norwegians [74], UK population [65], and Egyptians [75]. Two separate meta-analyses also indicated that PTPN22 C1858T is associated with susceptibility to JIA [76, 77]. However, it is not associated with JIA in Finish and Hungarian patients [78, 79]. These variations may be due to ethnic variations; however, methodological error in genotyping cannot be ruled out.
