IL12B encodes the IL12/23p40 protein, a common subunit of IL-12 and IL-23. IL-12 is a critical cytokine for proliferation and activation of type 1 helper T (Th1) cells.[51] IL-23 plays an essential role to maintain Th17 cells,[52] the important involvement of which in autoimmune diseases has been shown.[53] A previous Turkish study suggested

that patients with TAK displayed a higher level of IL-12p40 in their serum than a healthy population.[54] Future study should be addressed on correlation of IL-12p40 levels and disease activity. Interestingly, IL12B is also associated with psoriasis, inflammatory bowel diseases and leprosy.[55-58] In particular, rs6871626, the strongest susceptibility single nucleotide polymorphism (SNP) selleck chemicals in our study, is the same SNP associated with ulcerative colitis (UC) and leprosy. However, the risk allele is common for TAK and UC but opposite for leprosy. These results suggest that genetic studies confirmed the importance of Th1 and/or Th17 in pathophysiology in TAK.[59] The suggestive association between PSMG1 and TAK may also support overlapping of genetic factors between TAK and UC.[60] Since the neighbors of MLX in chromosome 17 are located in a gene-rich region,[61] it is unclear whether MLX is the gene responsible for TAK susceptibility. Dense mapping combined with functional analyses may reveal the true responsible gene

in this region. The involvement of FCGR2A/3A with TAK in a European population suggests the importance of immune-complex in pathophysiology of TAK. It is interesting because previous studies have not confirmed selleck compound the importance of autoantibody or B cell functions in TAK pathophysiology.[59] Macrophages and neutrophils expressing FCGR2A and 3A, are found in the aorta lesions of patients.[62] There have also been other genetic studies, but all of them addressed HLA alleles or non-HLA markers through candidate gene approaches. TNF-alpha, MYD88, PDCD1, PTPN22 and IL12B genes were examined,[63-67] but the IL12B gene was the only one demonstrating a suggestive association.

Cyclic nucleotide phosphodiesterase We have listed a summary of genetic studies for TAK in Table 1. It should be noted that most of the studies except for the two GWAS contained less than 200 subjects. This illustrates the difficulty in collecting samples due to the relatively low prevalence of the disease. Since recent GWAS shifted to trans-ethnic or multi-ethnic meta-analysis, summing up subjects from around the world would lead to the identification of multiple susceptibility genes to this disease. It is quite interesting that TAK and leprosy, a chronic infectious disease caused by Mycobacterium leprae, one of the mycobacterium species, share the same SNP in relation to their susceptibility. TAK has been believed to be one presentation of tuberculosis, an infection caused by M. tuberculosis.