title: Genetic variations of PD1 and TIM3 are differentially and interactively associated with the development of cirrhosis and HCC in patients with chronic HBV infection.
abstract: Cooperation or interaction of programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) molecules is more relevant than either molecule alone to immune dysfunction in chronic viral infection and cancers. This study simultaneously investigated polymorphisms at PD1 +8669 and TIM3 -1516 loci in 845 hepatitis B virus (HBV) chronically infected patients [151 asymptomatic carriers, 202 chronic hepatitis, 221 cirrhosis and 271 hepatocellular carcinoma (HCC)], 141 HBV infection resolvers and 318 healthy controls. Multivariate analysis showed that, in addition to gender, age, ALT, albumin and HBV DNA, PD1 +8669 genotype AA was associated with cirrhosis compared with patients without cirrhosis (OR, 2.410; P=0.001). TIM3 -1516 genotypes GT+TT, together with gender, age, ALT, AST, direct bilirubin, albumin and HBeAg status, were associated with HCC compared with cirrhosis patients without HCC (OR, 2.142; P=0.011). The combined carriage of PD1 +8669 AA/TIM3 -1516 GT or TT was higher in cirrhosis and HCC pooled patients than in patients without cirrhosis (OR, 2.326; P=0.020) and in HCC patients than in cirrhosis patients (OR, 2.232; P=0.013). These data suggest that PD1 and TIM3 polymorphisms may differentially and interactively predispose cirrhosis and HCC in chronic HBV infection.
authors.affiliation: Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061 Shaanxi, PR China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.forename: Guoyu
authors.initials: G
authors.lastname: Zhang
authors.forename: Qunying
authors.initials: Q
authors.lastname: Han
authors.forename: Pingping
authors.initials: P
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Xun
authors.forename: Yawen
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zeng
authors.forename: Cuiling
authors.initials: C
authors.lastname: Yang
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D000072597:Hepatitis A Virus Cellular Receptor 2; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D012307:Risk Factors
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D061026:Programmed Cell Death 1 Receptor