Study Of JAK1 Gene Polymorphisms In Primary Biliary Cholangitis In A Han Chinese Population Based On GWAS Results

Primary biliary cholangitis(PBC),formerly designated as primary biliary cirrhosis,is a chronic and progressive intrahepatic cholestatic disease that can ultimately progress to severe hepatic illnesses,including hepatic cirrhosis,hepatic failure,and even hepatocellular carcinoma.The disease predominantly affects middle-aged women.The combination of genetic and environmental factors is the main cause of the pathogenesis of PBC.The incidence of PBC in first-generation relatives is 100 times higher than that in the general population,and the genetic susceptibility of individuals is the main internal cause of PBC.The results of multiple genome-wide association studies(GWAS)for different ethnic groups further confirmed the strong genetic susceptibility of PBC,and they were significant differences among different ethnic groups.In order to study the genetic susceptibility of Han Chinese PBC population and to compare with other populations.This subject is carried out based on the previous GWAS result,all significant sites on JAK1 were analyzed and the two significant SNPs of JAK1: rs7531799 and rs4915675 were performed on association verification.According to the PBC diagnostic criteria recommended by“American Association for the Study of Liver Diseases”,1545 PBC cases and 2227 healthy controls are recruited for case-control study.The genotypes of SNP rs7531799 and SNP rs4915675 were detected by TaqMan-MGB probe real-time PCR.The data was statistically analyzed with IBM SPSS 19.0 software and Haploview 4.2 software.The results show that rs7531799 reaches the genome-wide significance level.It is suggested that JAK1 is likely to be a new genetic susceptibility gene of PBC in a Han Chinese population.Besides,rs7531799 accounts for JAK1 genetic susceptibility in a Han Chinese PBC population.This study is the first report to identify and verify JAK1 polymorphisms in a large-scale of a Han Chinese PBC populations.