Preliminary Screen Of The Susceptibility Genes Associated With The Pathogenesis Of Primary Biliary Cholangitis In East Zhejiang

Backgound: primary biliary cholangitis(PBC)is a kind of progressive intrahepatic cholestatic disease with autoimmunity.The etiology of PBC is complicated.Its pathogenesis has been presumed to involve multifactors,including immune,genetic and environmental factors.Many studies have shown that genetic susceptibility plays a crucial role in the pathogenesis of PBC and dozens of disease-related risk genes have been identified.However,genetic susceptibility of PBC is significantly different between different regions and different populations.Reports of susceptibility genes in east of Zhejiang are currently lacking.Objective: This study aimed to explore the susceptibility genes associated with the pathogenesis of PBC in east Zhejiang and provide new treatment ideas for targeted therapy of PBC in certain region.Methods: Screening of the condition data of PBC patients and their first-degree relatives from the eastern Zhejiang province who attended hospitals in Ningbo from January 2010 to September 2017.8 PBC probands and their 22 first-degree relatives who met the inclusion criteria were selected to form 8 PBC families.Peripheral venous blood samples were collected from subjects,3 ml each,for a total of 30 samples.The genomic DNA of the selected candidates was extracted and the whole exome sequencing method was used to screen for mutation sites.The mutation hazard prediction and gene function analysis were performed.Then the candidate mutation genes related to the disease were initially screened to explore the relationship between the mutation and the disease.The relationship between gene mutation and pathogenesis of PBC was analyzed in combination with gene function.Results: Sequenced by whole exome sequencing,the NUP93 gene c.315-316 T>A mutation and the SIGLEC11 gene c.455-456 C>A mutation were discovered in the family 1proband.These two missense mutations were likely to be pathogenic and harmful.And they were firstly discovered and have not been reported in the public database.The NCF2(rs13306575)gene c.436-437 G>A mutation was found on the chromosome 1 in the son and daughter of the family 4 proband.The mutation was also pathogenic and harmful.Gene function and bioinformatics analysis showed that mutations in these genes may be involved in the pathogenesis of PBC.Conclusion: NUP93,SIGLEC11,NCF2(rs13306575)may be involved in the pathogenesis of PBC.However,further study with more PBC cases is needed to confirm our preliminary finding.