Association between hepatitis B virus infection and HLA‐DRB1 genotyping in Shaanxi Han patients in northwestern China

Abstract

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The mechanism of susceptibility to chronic persistent HBV infection is not well clarified, while the outcome of HBV infection mainly depends on the host immune response. Human leukocyte antigen (HLA) class II molecule is an integral component of the immune response on which majority of host genetic studies have concentrated. Many different HLA class II alleles have been demonstrated to play roles in HBV infection. In this study, the association between HBV infection and HLA-DRB1 alleles in Han individuals in northwestern China was studied for the first time. Two hundred and fifty Shaanxi Han individuals were categorized into three different groups: the HBV-infected patient group (n = 108), the spontaneously cleared control group (n = 108) and the unexposed group (n = 34). DRB1*04, DRB1*09, DRB1*12 and DRB1*15 were the most common genotypes in all the groups. The allele frequencies of HLA-DRB1*03 [10.6% of HBV-infected patients vs 3.7% of spontaneously cleared controls, odds ratios (OR) = 3.10, Pc = 0.008, P < 0.05] and HLA-DRB1*07 (17.6% of HBV-infected patients vs 9.3% of spontaneously cleared controls, Pc = 0.016, OR = 2.09, P < 0.05) were markedly higher in the HBV-infected group. But the allele frequencies of HLA-DRB1*15 (6.9% of HBV-infected patients vs 13.4% of spontaneously cleared controls Pc = 0.039, OR = 0.48, P < 0.05) were obviously lower than that of the spontaneously cleared controls. The above data indicate that HLA-DRB1*03 and HLA-DRB1*07 are related to susceptibility to chronic HBV infection, and DRB1*15 is negatively related to persistence to chronic HBV infection among people in northwestern China. Similar results were got for DRB1*03 and 15 alleles between the HBV-infected patients (n = 108) and 46 HBV seronegative spouses of the HBV patients, who were high-risk group for HBV infection. The above results suggest that host HLA class II gene is an important factor in determination of the outcome of HBV infection.

Association of human leukocyte antigen-DRB1 alleles with chronic hepatitis B virus infection in the Han Chinese of Northeast China

“…We also found that the frequencies of the HLA-DRB1 * 04 and * 13 alleles in the HBV-infected patients were significantly lower than those in healthy controls, suggesting that these alleles may be associated with a reduced risk for the development of CHB even after infection with HBV. Our results agree with previous findings that the HLA-DRB1 * 04/ * 06, HLA-DRB1 * 11/ * 12, HLA-DRB1 * 1101/ * 1104 are associated with the clearance of HBV (16,(19)(20)(21). Association of the HLA-DRB1 * 13 with viral clearance is well established (22,23 (20).…”

“…We found that the frequency of HLA-DRB1 * 09 in the HBV-infected patients was significantly higher than that in the healthy controls, suggesting that the HLA-DRB1 * 09 alleles are associated with increased risk for the infection and progression of HBV and CHB in the Han Chinese of Northeast China. The results are consistent with a previous report (16), which showed a significantly higher frequency of HLA-DRB1 * 09 in CHB patients. To investigate the potential association of HLA-DRB1 genotypes and persistent infection of HBV in this population, we compared the frequencies of HLA-DRB1 alleles between Table III.…”

Role of HLA Allele Polymorphism in Chronic Hepatitis B Virus Infection and HBV Vaccine Sensitivity in Patients from Eastern Turkey

“…Similar protective effects were not observed in the present study or in another study on Turkish patients (Karan et al 2002). Yang et al (2007) reported that HLA-DR13 was observed at a higher rate in a group that spontaneously developed antibody, but this increase was not statistically significant. In the same study, in cases where the HLA viral load was great, the HLA-DRB1*07 allele was associated with the onset of chronic HBV infection.…”

Relationship betweenHLA-DRgene polymorphisms and outcomes of hepatitis B viral infections: A meta-analysis

“…The Egger's test results suggested that publication bias in our meta-analyses of HLA-DR alleles was not remarkable except for the three subgroup meta-analyses. As shown in Table 2 Hohler et al [16] 1997 English Caucasian PCR-SSP 24 NA 70 Outpatients 7 3 Ahn et al [18] 2000 English Korean PCR-SSP 243 156 males, mean age: 41 yr 83 53 males, mean age: 35 yr 8 4 Chen et al [42] 2002 Chinese Chinese Han PCR-SSP 56 43 males, mean age: 47.6 yr 30 22 males, mean age: 38.7 yr 7 5 Akcam et al [33] 2002 English Iran PCR-SSP 30 20 males, mean age: 35.9 yr 30 7 males, mean age: 31.0 yr 7 6 Jiang et al [21] 2003 English Chinese Han PCR-SSP 30 24 males, mean age: 33.2 yr 52 43 males, mean age: 33.46 yr 7 7 Meng et al [20] 2003 English Chinese Han PCR-SSP 56 22 males, mean age: 38.7 yr 30 43 males, mean age: 47.6 yr 7 8 Wu et al [19] 2004 English Chinese Han SSOPH 324 169 males, mean age: 39.1 yr 98 66 males, mean age: 50.9 yr 8 9 Wu et al [19] 2004 English Taiwanese 14 Yang et al [35] 2007 English Chinese Han PCR-SSP 108 Age and sex matched 108 90 males, 58 LC, 24 HCC 7 15 Song et al [44] 2007 Chinese Chinese Han PCR-SSP 102 63 males, mean age: 33.9 yr 276 168 males, 77 LC, 106 ASC 5 14 Zhu et al [36] 2007 English Chinese Han PCR-SSP 133 63 males, mean age: 37 yr 151 120 males, mean age: 40 yr 7 15 Hwang et al [37] 2007 16 Kummee et al [38] 2007 English Thai PCR-SSP 100 48 males, mean age: 51.0 yr 150 80 males, mean age: 30.9 yr 8 17 Cho et al [39] 2008 English Korean PCR-SSP 80 60 males, mean age: 47.9 yr 384 283 males, mean age: 41.0 yr 8 18 Remezani et al [40] 19 Albayrak et al …”

“…These 18 articles were published from 1995 to 2011 with 15 in English [16,[18][19][20][21][32][33][34][35][36][37][38][39][40][41] and three in Chinese [42][43][44] . Of them, nine studies were on Han Chinese populations [19][20][21][34][35][36][42][43][44] and 10 studies on other race (Gambia [32] , Caucasian [16] , Korean [18,37,39] , Iran [33,40] , Thai [38] and Turkish [41] ). Besides, one publication contained two individual case-control studies from two different ethnic populations (Chinese Han and Taiwanese aborigines [19] ).…”