Association of Interleukin-1β and Gene Polymorphisms with Liver Pathogenesis in Hepatitis B Virus Infection among Eastern Indian Population

Abstract

Background: Interleukin-1β (IL-1β) is an important member of the family of the proinflammatory cytokines that modulate outcome of hepatitis B virus (HBV) infection.

Objectives: This study was designed to investigate the relationship between the polymorphic genotypes of the interleukin-1β (IL-1β) promoter region and the interleukin-1 receptor antagonist gene (IL-1RN) and disease outcome in HBV-infected individuals.

Methods: DNA was extracted from 395 study subjects including HBV carriers with varying clinical presentations, as well as healthy controls and spontaneously recovered cases (SRC). Polymorphisms in IL-1β (at position -511) and IL-1RN (variable nucleotide tandem repeats, VNTR) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR based assay respectively.

Results: Among the study subjects, different IL-1β (at position -511) (CC, CT and TT) and IL-1RN (1/1, 1/2, 2/2 and 1/3) polymorphic genotypes were found at variable proportions. Logistic regression analysis revealed, no notable difference at the level of IL-1β promoter (P = 0.244; OR = 0.78; 95% CI = 0.52-1.18) or IL-1RN genotype polymorphism (P = 0.840; OR = 1.03; 95% CI = 0.78-1.36) among the HBV carriers and controls or SRC cases. Pairwise proportion testing showed, IL-1β -511 genotype CC was significantly higher among asymptomatic carriers (ASC) in comparison with liver cirrhosis (LC) patients (P value = 0.028) and healthy control group (P-value = 0.036). IL-1RN genotype 2/2 was considerably higher in LC group than SRC as well as control group. Combinations of IL-1β (-511) and IL-1RN polymorphisms were associated with disease progression, such as CC-1/2 with ASC and TT-2/2 with LC.

Conclusion: IL-1β polymorphisms are found to be associated with disease severity. Different polymorphic combinations are associated with degree of disease severity. Overall this is the first report from Eastern India, which shows association of IL-1β polymorphisms with HBV-related hepatic complications.

Keywords: ASC, asymptomatic carriers; CLD, chronic liver disease; Eastern India; HBV; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; IL-1RN, interleukin-1 receptor antagonist gene; IL-1β, interleukin-1β; LC, liver cirrhosis; LR, logistic regression; PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism; SNP, single nucleotide polymorphisms; SRC, spontaneously recovered cases; USG, ultrasonography; VNTR, variable nucleotide tandem repeats; cirrhosis; interleukin polymorphisms.

Figure 1

Correlation between HBV viral load and IL-1β (−511) genotypes are presented in the figure. Boxes indicate upper and lower quartiles; horizontal lines inside boxes indicate median values.