CTLA-4, ICOS, PD1 and PTPN22 Gene Polymorphisms and Susceptibility to Autoimmune Hepatitis Type 1

Autoimmune hepatitis type 1 (AIH-1) is a progressive inflammatory liver disorder in which HLA Class II gene polymorphism prevails as the most important genetic risk. However, other gene polymorphisms have been associated with this disease. The single nucleotide polymorphisms of four candidate genes (CTLA-4 +49A/G, ICOS c.1564 T/C, PD1.3 G/A, PTPN22 1858C/T) were selected in this study. One-hundred and ninety (190) mestizo Venezuelan unrelated individuals grouped in AIH-1 patients (n=70) and healthy subjects (n=120) were evaluated. Our results showed significantly increased frequency of the PTPN22 1858 C/T (p= 0.0014; pc= 0.0042; OR= 8.7; 99%CI: 1.82-41.54) and ICOS c.1564 T/C (p= 0.070; pc=0.21; OR= 2.08; 95%CI: 1.09-3.93) genotypes in the patient population compared to control group. There was no significant association between CTLA-4 +49A/G and PD1.3 G/A genotypes in both groups. In addition, the PTPN22 1858C/T polymorphism was associated to cirrhosis, treatment relapse, increased IgG levels and co-existence of other autoimmune diseases. Furthermore, the ICOS c.1564 T/C polymorphism was related to higher levels of globulins, IgG and presence of ANA. Conclusion: this data suggest for the first time, that PTPN22 1858 C/T and ICOS c.1564 T/C gene polymorphisms are associated with the development of AIH-1.