The association between PIN1 genetic polymorphisms and the risk of chronic hepatitis B and hepatitis B virus-related liver cirrhosis

Abstract

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) reportedly plays a crucial role in tissue inflammation and tumourigenesis. Our previous studies have demonstrated that PIN1 gene polymorphisms are significantly related to the pathogenesis of hepatitis B virus (HBV)-related liver cancer in a Guangxi population. As chronic hepatitis B (CHB), liver cirrhosis (LC), and liver cancer are development processes, we further investigated whether any relationship exists between PIN1 gene polymorphisms and the risk of CHB and HBV-related LC. We used the polymerase chain reaction restriction fragment length polymorphism and the deoxyribonucleic acid sequencing method to analyze 3 common single-nucleotide polymorphisms (SNPs) (rs2233678, rs2233679, and rs2233682) of the PIN1 gene in 192 CHB patients, 171 HBV-related LC patients, and 201 healthy controls in this research. The results revealed that carriers of the rs2233682 A allele had a significantly decreased risk of HBV-related LC (LC vs. controls: odds ratio [OR] = 0.262, 95% confidence interval [CI] = 0.071-0.959, P = .043; LC vs. CHB: OR = 0.198, 95% CI = 0.049-0.803, P = .023). Similar relationships were observed for the PIN1 rs2233682 GA genotype among the groups (LC vs. controls: OR = 0.248, 95% CI = 0.067-0.919, P = .037; LC vs. CHB: OR = 0.184, 95% CI = 0.044-0.773, P = .021). This reduced risk was more obvious in older CHB patients (age ≥50 years). No such correlations were found for PIN1 rs2233678 and rs2233679. However, the haplotypes constructed from these SNP (GCA for controls and CCG for CHB) were associated with a significantly decreased risk of HBV-related LC. In summary, the findings of this study suggest that the PIN1 rs2233682 A allele might be related with a decreased risk of HBV-related LC in a Guangxi population.

Genetic variants that associate with cirrhosis have pleiotropic effects on human traits

“…Stage 3 analysis included replicating SNPs as well as SNPs that have been previously reported to associate with cirrhosis in subpopulations, as described in the introduction (Table ) . As above, we included only SNPs with minor allele count >6 in the European populations of UKBB and MGI, which corresponded to minor allele frequency >0.006.…”

“…have been previously reported to associate with cirrhosis in subpopulations, as described in the introduction (Table S1). 5,8,9,[12][13][14][15][16][22][23][24][25][26][27][28][29][30][31][32] As above, we included only SNPs with minor allele count >6 in the European populations of UKBB and MGI, which corresponded to minor allele frequency >0.006. For stage 3 SNPs, a cut-off of P < .05 in either UKBB or MGI was used because there was prior knowledge of their role in liver disease and fibrosis.…”

The molecular mechanisms of peptidyl-prolyl cis/trans isomerase Pin1 and its relevance to kidney disease

“…In clinical research, Pin1 has emerged as an independent predictor of liver fibrosis, with serum Pin1 levels being correlated with the histopathological stages of liver fibrosis in NASH ( Cengiz et al, 2014 ). Additionally, genetic polymorphisms in PIN1 have been linked to the risk of hepatitis B virus-related liver cirrhosis among HBV-infected patients in Guangxi, China ( Huang et al, 2018 ). Pin1 has been found to be upregulated in NASH mouse models and promotes liver fibrosis through various pathways ( Nakatsu et al, 2012 ; Yang et al, 2014 ; Kim et al, 2016 ).…”