Study IL- 35 Level and Fibronectin Type Ⅲ Domain Containing Protein 5 \ Irsin (FNDC5 rs3480) Gene Variations in Chronic Hepatitis B.

Hepatitis B virus (HBV) infection is a serious public health problem worldwide, with approximately 2 billion people having a history of HBV infection and 350 million of them suffering from chronic HBV infection (1).

Although the host factors (such as infection age, gender and immune status), viral and environmental factors are thought to be involved in affecting the development of CHB. The mechanisms underlying the different clinical outcomes of HBV infection have not been fully understood. Studies indicated that host genetic factors play a critical role in the development of HBV infection, especially single nucleotide polymorphisms (SNPs), is regarded to be one of the determinants for this clinical heterogeneity(2,3). Some polymorphisms have been reported to be involved in susceptibility to CHB in disease severity and progression, or disease prognosis (4,5).

Irisin is encoded by the FNDC5 gene, whose expression is controlled by the peroxi- some proliferator activated receptor gamma coactivator 1 alpha (PGC-1α). PGC-1α is a transcriptional co-activator which does not bind directly to DNA. Studies indicated that the estrogen-related receptor alpha (ERRα) could be a factor that plays a role in PGC-1α binding to DNA. ERRα is encoded by the ESRRA gene and is an orphan nuclear receptor, which has two domains. One of them allows the interaction with DNA, and the second one with a ligand. The ERRα structure is similar to that of the estrogen receptor alpha (ERα), but this receptor does not bind to natural estrogens. ERRα interacts with a canonical sequence of the estrogen response elements (ERRE). ERRα and ERα could compete with each other to bind to similar DNA elements. Together, ERRα binds to DNA, in complex with PGC-1α, to regulate the activity of genes such as FNDC5 (6).