Association of the Interleukin-1 beta and Interleukin-1 Receptor Accessory Protein Gene Polymorphisms with Persistent Hepatitis B Virus Infection and Hepatocellular Carcinoma

Abstract

"Background & Aims: The reasons for persistent hepatitis B virus infection (HBV) are unknown, but they are probably related to host immune factors. Interleukin-1β (IL-1β) plays significant roles in inflammation and immune defense via IL-1 receptor accessory protein (IL-1RAcP). We investigated whether genetic polymorphisms of IL-1B and IL-1RAcP genes are associated with persistent HBV infection and the presence of hepatocellular carcinoma (HCC).

Methods: We enrolled a total of 292 patients with chronic HBV infection (111 with chronic hepatitis, 95 with liver cirrhosis and 86 with HCC) and 107 healthy individuals who recovered from HBV infection. We assessed 28 SNPs in IL-1B and IL-1RAcP genes by using Illumina’s Sentrix array matrix chip.

Results: Four SNPs of IL-1B (-2023G>C, -581T>C, 289T>C, 3340A>G) and six SNPs of the IL-1RAcP (-51668T>A, -8261T>C, -8183A>G, -256C>T, 59264G>A, 65445A>G) showed biallelic polymorphism. IL-1B -2023 C allele, IL-1RAcP -8261 T allele and -8183 A allele were significantly associated with persistent HBV infection (OR, 1.63, P = 0.03, OR, 0.64, P <0.01 and OR, 0.20, P = 0.01, respectively). IL-1B 289 C allele was marginally associated with an increased risk for the presence of HCC (OR, 1.55, P = 0.04). On the haplotype analysis, IL-1B -2023C/-581C/2893C haplotype and IL-1RAcP -8261T/-8183A haplotype were associated with persistent HBV infection. There is no significant association between the haplotypes of IL-1B/IL-1RAcP and the presence of HCC.

Conclusions: The genetic polymorphisms of IL-1B -2023 C allele, IL-1RAcP -8261 T allele and -8183 A allele are probable host factors for persistent HBV infection.

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