HLA-DQ polymorphisms have multiple effects on HBV infection characteristics
medwireNews: Two single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA)-DQ gene have distinct impacts on the clinical characteristics of patients with chronic hepatitis B virus (HBV) infection, Japanese research shows.
The first, rs2856718, is associated with hepatocellular carcinoma (HCC) development, as well as other markers of HBV infection, in hepatitis B e antigen (HBeAg)-negative patients, while the second, rs7453920, is associated with hepatitis B surface antigen (HBsAg) levels.
“This variation may be attributed to differences in the roles played by these SNPs in HLA class II-mediated immune responses,” write Kentaro Yoshioka and colleagues from Meijo University in Nagoya.
Yoshioka and team genotyped 299 patients with chronic HBV to examine the effects of the two SNPs on the development of HCC and markers of HBV infection.
Among the 224 patients who were HBeAg-negative, those with rs2856718 AG or GG genotypes had significantly lower hepatitis B core-related antigen (HBcrAg) levels (p=0.0184), required less frequent treatment with nucleos(t)ide analogs (p=0.0433), and were less likely to develop HCC (p=0.0256) than those with genotype AA.
In addition, HCC development was positively associated with rs2856718 genotype AA (p=0.0254) on multivariate analysis.
“This result corresponds to the previously reported association between rs2856718 and HCC development, although there have also been three studies that did not find any such association,” Yoshioka et al remark.
They suggest: “This discordance of results may be attributed to the differences in the disease phases and genetic characters of the population studied.”
For rs7453920, HBeAg-negative patients with the GG genotype had significantly lower HBsAg levels (p<0.0001), a higher prevalence of HBV genotype C (p=0.0063), a lower prevalence of the wild-type basal core promoter (BCP) region (p=0.0045), and a higher prevalence of a family history of chronic HBV infection (p=0.0147) than those with the AA or AG genotype.
And on multivariate analysis, HBsAg levels (p=0.0050) and prevalence of the wild-type BCP region (p=0.0050) were positively associated with the rs7453920 AA and AG genotypes, while a negative association was observed with HBcrAg levels (p=0.0260)
The only significant association found among the 75 HBeAg-positive patients was that those with rs2856718 genotype AG or GG had a significantly lower prevalence of the wild-type BCP region than those with genotype AA (p=0.0180).
Yoshioka and co-authors note that the small sample size is a limitation of the study.
They therefore conclude in Hepatology Research that “[f]urther studies with larger sample sizes are needed” to clarify the associations observed and the mechanisms behind them.
By Laura Cowen
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