Polymorphisms near interleukin 28B gene are not associated with hepatitis B virus clearance, hepatitis B e antigen clearance and hepatocellular carcinoma occurrence.

Polymorphisms near the IL28B gene have been proposed to be strongly associated with treatment response and the rate of spontaneous clearance of hepatitis C virus infection, and treatment response of hepatitis B virus (HBV) infection. In this study, we aimed to determine whether these polymorphisms could affect natural courses of HBV infection. Genetic variations were identified through direct DNA sequencing using TaqMan assay in 1,439 patients with past or present HBV infection. Subjects included 404 spontaneously recovered patients, 313 chronic hepatitis B (CHB) patients, 305 liver cirrhosis (LC) patients and 417 hepatocellular carcinoma (HCC) patients. Three polymorphisms near the IL28B gene, rs8099917T>G, rs12979860C>T and rs12980275A>G, were identified. Associations between these polymorphisms and HBV clearance, hepatitis B e antigen (HBeAg) clearance as well as HCC occurrence among patients were analyzed using logistic regression analyses adjusted for age and gender. There were no significant associations between these polymorphisms and the HBV clearance both in CHB and LC groups. Similarly, these polymorphisms showed no significant associations with HBeAg clearance and the occurrence of HCC either. No significant association was identified between polymorphisms near the IL28B gene and the natural courses of chronic HBV infection, including the HBV clearance and HCC occurrence.

Lee DH ，Cho Y ，Seo JY ，Kwon JH ，Cho EJ ，Jang ES ，Kwak MS ，Cheong JY ，Cho SW ，Lee JH ，Yu SJ ，Yoon JH ，Lee HS ，Kim CY ，Shin HD ，Kim YJ ... -  《-》

Gene polymorphisms of interleukin 28B and the risk to chronic hepatitis B virus infection in Thai.

In this study, we aimed to evaluate the effect of two single nucleotide polymorphisms (SNPs) of interleukin 28B (IL28B) (rs12979860C/T and rs8099917G/T) on chronic hepatitis B virus (CHB) infection in Thai population. We studied 375 subjects: 83 CHB with hepatocellular carcinoma (HCC) patients, 128 CHB without HCC and 164 individuals with self-limited HBV infection, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan allelic discrimination assay. Results revealed significant risk of IL28B rs8099917T allele associated with CHB without HCC compared with self-limited HBV [odds ratio (OR) (95% confidence interval (CI)) = 2.56 (1.08-6.28), P = 0.019]. The effect of this T allele was similar to that of an autosomal recessive gene in the presence of TT genotype compared with GG and GT genotype [OR (95% CI) = 2.70 (1.11-6.77), P = 0.016, P (logistic regression) = 0.048]. The two locus haplotype analysis of the two IL28B SNP loci did not show any association with CHB (P > 0.05). In conclusion, these results suggested a IL28B rs8099917T allele predispose for susceptibility to chronic HBV infection but not leading to HCC in Thai population.

Kimkong I ，Chankaew J ，Kunanopparat A ，Hirankarn N ，Tangkijvanich P ... -  《-》

Impacts of human leukocyte antigen DQ genetic polymorphisms and their interactions with hepatitis B virus mutations on the risks of viral persistence, liver cirrhosis, and hepatocellular carcinoma.

Human leukocyte antigen (HLA)-DQ genetic polymorphisms have been associated with chronic hepatitis B virus (HBV) outcomes. We aimed to determine impacts of HLA-DQ polymorphisms and their interactions with HBV mutations on the risks of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). rs2856718 (A>G) and rs9275319 (A>G) were genotyped in 1342 healthy controls, 327 HBV surface antigen (HBsAg) seroclearance subjects, 611 asymptomatic HBsAg carriers (ASCs), 1144 chronic hepatitis B (CHB) patients, 734 LC patients, and 1531 HCC patients using quantitative PCR. HBV mutations were detected by direct sequencing. Logistic regression analyses were utilized to assess the factors and/or multiplicative interactions significantly associated with liver diseases. rs9275319 variant genotypes were inversely associated with HBV persistence compared to HBV natural clearance subjects. rs2856718 variant genotypes significantly increased LC risk compared to ASCs plus CHB patients (GG vs. AA: odds ratio [OR], 1.52, 95% confidence interval [CI], 1.17-1.97 and AG+GG vs. AA: OR, 1.27; 95% CI, 1.04-1.54) and decreased HCC risk compared to HCC-free HBV-infected subjects (AG vs. AA: OR, 0.76; 95% CI, 0.65-0.89 and AG+GG vs. AA: OR, 0.78, 95% CI, 0.68-0.90). rs2856718 variant genotypes were significantly associated with an increased frequency of HBV A1726C mutation, a LC-risk, HCC-protective mutation, in genotype C. A rs9275319 variant genotype (GG) was significantly associated with an increased frequency of preS1 start codon mutation, an HCC-risk mutation, in genotype C. The interaction of rs2856718 AG+GG genotype with T1753V, a HCC-risk mutation, significantly reduced LC risk, with an OR of 0.26 (95% CI, 0.09-0.78); whereas the interaction of rs2856718 AG genotype with C1673T, a LC-risk mutation, significantly increased HCC risk, with an OR of 2.80 (95% CI, 1.02-7.66) in genotype C HBV-infected subjects. Conclusively, the HLA-DQ polymorphisms affect the risks of LC and HCC differently in chronic HBV-infected subjects, possibly via interacting with the HBV mutations.

Ji X ，Zhang Q ，Li B ，Du Y ，Yin J ，Liu W ，Zhang H ，Cao G ... -  《-》

SPP1 polymorphisms associated with HBV clearance and HCC occurrence.

Shin HD ，Park BL ，Cheong HS ，Yoon JH ，Kim YJ ，Lee HS ... -  《INTERNATIONAL JOURNAL OF EPIDEMIOLOGY》

TGFBR3 polymorphisms and its haplotypes associated with chronic hepatitis B virus infection and age of hepatocellular carcinoma occurrence.

Hepatocellular carcinoma (HCC) is one of the most common cancers and is mainly caused by viral infections including hepatitis B virus (HBV). Recently, the decreased expression level of the transforming growth factor, beta receptor III (TGFBR3) gene, has been implicated in HCC and other human cancers. This study investigated whether TGFBR3 polymorphisms might be associated with HBV clearance and HCC occurrence. This study identified 27 single nucleotide polymorphisms (SNPs) in the exon, promoter, and exon-intron boundary regions of TGFBR3 by resequencing in 24 individuals. Then, 9 SNPs in the promoter and exons of the gene were genotyped from 1,065 Koreans composed of 637 chronic carriers (CC) and 428 spontaneously recovered (SR) subjects. Two SNPs, rs1805113 (Phe676Phe) in exon 13 and rs1805117 in 3'-UTR (p = 0.009 and p = 0.008, respectively) were significantly associated with HBV clearance. In addition, Cox relative hazards analyses revealed that haplotype BL2_ht2 showed a significant association with the age of HCC occurrence among chronic HBV patients (relative hazard = 1.38; p = 0.007). Our findings suggest that TGFBR3 polymorphisms and its haplotypes might be associated with HBV clearance and age of HCC occurrence.

Kim JH ，Yu SJ ，Park BL ，Cheong HS ，Pasaje CF ，Bae JS ，Lee HS ，Shin HD ，Kim YJ ... -  《-》