While other studies have demonstrated that HLA-DP SNPs rs3077 and rs9277535 are strongly associated with chronic hepatitis B infection [13], [14], [15], [16], [17], selleck [18], [19], [20], [21], to our knowledge, the present study is the first study to determine the association between rs9277378 and chronicity of HBV infection. Although it is possible that the authentic effect of rs9277378 polymorphism may be due to its high LD with rs9277535, our findings with rs9277378 suggested that more SNPs (or combination of SNPs) in the HLA-DP regions may be associated with HBV infection. Data on the association of HLA-DP variations with chronic HBV infection are relatively scarce. In one study with 201 Caucasian chronic HBV carriers and 235 controls, the rs3077 T allele has also been identified to be protective against chronic HBV infection [18].

However, in that study, the rs3077 T protective allele was the major allele in the Caucasian cohort. This is consistent with the data from the HapMap project, which show that the frequencies of the protective alleles for rs3077 (T), rs9277378 (A) and rs3128917 (T) were higher in people with European ancestry than in the African and Asian populations [22]. Taken together, all these findings of HLA-DP genomic variations may shed light on the difference in the geographic distribution of HBV infection: it is possible that the lower prevalence of chronic HBV infection in the European/Caucasian populations is due to the higher prevalence of the protective HLA-DP alleles.

Similarly, the high prevalence of chronic HBV infection in the Asian/African populations is likely due to the lower prevalence of the protective HLA-DP alleles. However, it should be noted that other factors, apart from HLA-DP variations, are also associated with chronicity of HBV infection. If the HLA-DP variations were the sole decisive factors for chronicity, the prevalence of chronic hepatitis B would have been much more than 10% in the Chinese. Moreover, a certain proportion of Asian/Chinese who possess the risk HLA-DP alleles may not have contacted HBV in their life time. Thus, many other factors, such as viral, environmental and other host genetic factors, are likely to be associated with chronicity of HBV infection. Nevertheless, the findings from the present as well as other genetic association studies, suggest that HLA-DP variations are probably one of the genetic factors which plays an important role in the development Brefeldin_A of chronicity of HBV infection. Clearance of HBV infection is associated with a high level of CD4+ T cells response [24], [25]. HLA-DP molecules, belonging to HLA class II, are involved in antigen presentation to CD4+ T helper cells.