HLA-DQA1基因多态性和HBV感染结局的关联

目的 探讨人类白细胞抗原(HLA)DQA1基因多态性与乙型肝炎病毒(HBV)感染临床结局的关联.方法 临床收集慢性乙型肝炎(120例)、慢性HBV携带者(60例)、自限性HBV感染者(60例)三组病例,前两组诊断均经肝活检证实.聚合酶链反应序列特异性引物(PCR-SSP)法检测HLA-DQA1基因型,比较组间基因频率的差异.结果 (1)HLA-DQA1*0201在慢性乙型肝炎组的分布频率显著高于自限性HBV感染组(38.3% vs 5.8%,P<0.001,A=10.04,95% CI:4.48～22.48);HLA-DQA1*0102的分布频率显著低于自限性HBV感染组(9.6% vs 36.7%,P<0.001,A=0.183,95%CI:0.10～0.32).(2)HLA-DQA1*0201在慢性乙型肝炎组的分布频率显著高于慢性HBV携带者组(38.3% vs 7.5%,P<0.01,A=7.667,95% CI:3.7～15.87);HLA-DQA1*0102的分布频率显著低于慢性HBV携带者(20% vs 9.6%.P<0.01,A=0.424,95% CI:0.23～0.79).结论 HLA-DQAI基因多态性影响HBV感染临床结局,其中DQA1*0102呈保护作用,DQA1*0201可能促进HBV感染的慢性化和肝炎的发生.     

HLA-DRB1及HLA-DQA1单倍型与乙型肝炎病毒感染结局的关联研究

目的探讨中国北方汉族人群HLA-DRB1、DQA1单倍型与乙型肝炎病毒（hepatitis B virus，HBV）感染不同结局的关系。方法采用序列特异性引物聚合酶链反应（sequence specific primers polymerase chain reaction，PCR-SSP）技术检测HLA-DRB1、DQA1等位基因，并比较207例慢性乙型肝炎患者，212名无症状HBV慢性携带者（HBV携带者），148例自限性HBV感染者的单倍型频率。结果自限性HBV感染组单倍型DRB1＊04-DQA1＊0301的频率为10．03％，显著高于慢性乙肝组的3．66％（P=0．0005）：DRB1＊15／＊16-DQA1＊0102的频率为6．80％，显著高于慢性乙肝组的1．94％（P=0．0012）和无症状HBV慢性携带者组的1．65％（P=0．004）；DRB1＊04-DQA1＊0302单倍型在慢性乙型肝炎组的频率为3．10％，明显高于自限性HBV感染组的0．39％（P=0．0077）。结论HLA-DRB1、DQA1单倍型与个体感染HBV后的不同结局存在显著关联。     

HLA-DRBl＊04等位基因多态性与乙型肝炎病毒感染结局关联分析

目的从分子遗传学角度探讨乙型肝炎病毒（hepatitis B virus，HBv）感染结局与GLA—DRBl＊04等位基因的相关性。方法采用聚合酶链反应一序列特异性引物（polymerase chain reaction-sequence specific primers，PCR-SSP）技术检测HLA-DRBl＊04等位基因，并比较106例无症状HBV携带者（HBV携带组），93例慢性乙型肝炎患者、77例乙肝肝硬化者、102例HBV感染后自然恢复者（对照组）HIA-DRBl＊04等位基因频率及HBV不同复制状态下HLA-DRBl＊04等位基因频率。结果HBV携带组、慢性乙肝组、乙肝肝硬化组HLA-DRBl＊04等位基因频率高于对照组（分别为25．94％、26．34％、27．92％和14．22％，P〈0．01）；HLA—DRBl＊0401基因频率高于对照组（分别为20．91％、24．49％、22．09％和8．62％，P均〈0．05）；HLA-DRBl＊0405基因频率较对照组低（3．64％、2．04％、3．49％和15．52％，P〈0．01、0．01、0．05）。各病例组之间HLA—DRBl＊04等位基因频率差异无统计学意义（P〉0．05）。HBV不同复制状态HLA-DRBl＊04等位基因频率差异无统计学意义（P〉O．05）。结论HLA-DRBl＊04是决定HBV感染结局的因素之一，但不影响HBV在体内复制。     

HLA-DRB1*04等位基因多态性与乙型肝炎病毒感染结局关联分析

目的从分子遗传学角度探讨乙型肝炎病毒(hepatitis B virus,HBV)感染结局与HLA-DRB1*04等位基因的相关性。方法采用聚合酶链反应-序列特异性引物(polymerase chain reaction-seque nce specific primers,PCR-SSP)技术检测HLA-DRB1*04等位基因,并比较106例无症状HBV携带者(HBV携带组),93例慢性乙型肝炎患者、77例乙肝肝硬化者、102例HBV感染后自然恢复者(对照组)HLA-DRB1*04等位基因频率及HBV不同复制状态下HLA-DRB1*04等位基因频率。结果HBV携带组、慢性乙肝组、乙肝肝硬化组HLA-DRB1*04等位基因频率高于对照组(分别为25.94%、26.34%、27.92%和14.22%,P<0.01);HLA-DRB1*0401基因频率高于对照组(分别为20.91%、24.49%、22.09%和8.62%,P均<0.05);HLA-DRB1*0405基因频率较对照组低(3.64%、2.04%、3.49%和15.52%,P<0.01、0.01、0.05)。各病例组之间HLA-DRB1*04等位基因频率差异无统计学意义(P>0.05)。HBV不同复制状态HLA-DRB1*04等位基因频率差异无统计学意义(P>0.05)。结论HLA-DRB1*04是决定HBV感染结局的因素之一,但不影响HBV在体内复制。     

The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection

Background

Infection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections.

Methods

This study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interleukin-10, and DQB1 mRNA expression. A meta-analysis was also performed using relevant case–control studies that evaluated the associations of HLA-DQB1 alleles with HBV infection and clearance.

Results

We found that HLA-DQB1*06:03 protected against HBV infection. Levels of IFN-γ and IL-4 were significantly elevated in HBV cases with HLA-DQB1*06:05 (vs. HLA-DQB1*05:03), and the HBV group had higher DQB1 mRNA expression than the healthy control group with HLA-DQB1*05:03 and HLA-DQB1*06:02. The meta-analysis revealed that HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01 were risk factors for HBV infection susceptibility, while HLA-DQB1*05:01, HLA-DQB1*06:03, and HLA-DQB1*06:04 protected against HBV infection. Spontaneous HBV clearance was associated withHLA-DQB1*06:04, while chronic HBV infection was associated with HLA-DQB1*02:01 and HLA-DQB1*05:02.

Conclusion

DBQ1 typing can be used to identify patients who have elevated risks of HBV infection (i.e., patients with HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01) or elevated risks of chronic HBV infection (i.e., patients with HLA-DQB1*02:01 and HLA-DQB1*05:02).

     

Role of G protein beta3 subunit C825T and HLA class II polymorphisms in the immune response after HBV vaccination

The G protein beta3 (GNB3) subunit and HLA are candidate genes predictive of immune response capacity. We therefore studied the influence of both gene systems on cellular and humoral immunity against hepatitis B virus (HBV) in 79 HBV booster-vaccinated healthy volunteers and an independent group of 77 probands after HBV basic immunization. Following booster vaccination, lymphocyte in vitro proliferation after stimulation with HBV surface antigen was 2.5-fold increased in GNB3 825T (TC + TT) vs CC allele carriers (P = 0.01) and was not influenced by HLA-DRB1 or DQB1 alleles. In addition, anti-HBs antibody titers in both groups were 2-fold increased in TC vs CC and decreased in TT vs CC allele carriers. However, antibody titers after HBV booster immunization were elevated in HLA-DQB1*0301 carriers (P corrected = 0.027). In summary, the GNB3 825T allele appears as a marker particularly predictive of cellular and HLA-DQB1*0301 of humoral immune responses following HBV vaccination.     

HLA-DRB1*10与中国人慢性乙肝关联

目的研究ＨＬＡ－ＤＲＢ１基因与乙肝的关联,探讨可能由病毒感染继发的自身免疫反应导致疾病发展的主要原因,为乙肝的病因学及预后估计提供免疫学方面的资料。方法在我国北方地区随机选择５４名慢性乙肝患者,用ＰＣＲ／ＳＳＰ方法进行ＨＬＡ－ＤＲＢ１等位基因分型,对照组为同地区９２名健康人。采用疾病和ＨＬＡ相关分析软件进行数据处理。结果病人组ＨＬＡ－ＤＲＢ１＊１０基因频率明显增高为２５．９％（ＲＲ＝１０．３８,Ｐｃ＝０．００１）,其它等位基因频率在实验组与对照组间差异无显著性。结论ＨＬＡ－ＤＲＢ１＊１０基因与中国北方人群慢性乙肝关联     

Association between HLA class II alleles and hepatitis B virus infection in Transylvania,Romania

ABSTRACT

Infection with hepatitis B virus (HBV) is a major problem worldwide. The major histocompatibility complex plays an essential role in host immunity and can help eliminate the HBV of infected hepatocytes. Our study aimed to determine the role of certain human leukocyte antigen (HLA) class II molecules (i.e. HLA-DRB1 and HLA-DQB1) in the persistence or removal of HBV. Sixty patients confirmed to be HBV-positive via real-time polymerase chain reaction (PCR), i.e. people with chronic active hepatitis, were included in the study along with a control group of 100 healthy individuals without evidence of HBV infection. The DNA was subsequently used to determine HLA-DRB1 and HLA-DQB1 low-resolution typing genetic profile via PCR amplification. The univariate analysis performed revealed significant association of the HLA-DRB1*03 and HLA-DQB1*05 alleles to the infected persons (study group), while HLA-DRB1*01 was shown to be protective against HBV infection. To our knowledge, this is the first Romanian study associating HLA with HBV, and it can provide valuable insight concerning the relationship between genetic factors and immune response in the sampled population.     

山西省家族性乙型肝炎病例中HLA-DRB1基因位点的分析

目的 探讨HLA-DRB1等位基因多态性与家族性乙型肝炎之间的关系.方法 采用聚合酶链反应-特异性序列寡核苷酸（PCR-SSO）探针基因分型技术结合荧光磁珠流式检测仪,对151例家族性乙肝人群的HLA-DRB1基因位点进行了分析.结果 HLA-DRB1＊0701在慢乙肝组的等位基因频率（17.8%）明显高于正常对照组（7.4%）,差异有统计学意义（P＜0.05,A=1/0.367=2.725）;HLA-DRB1＊0401/0403/0405及HLA-DRB1＊1301/1302在正常对照组的等位基因频率（16.2%;4.4%）明显高于慢乙肝组（5.1%;0）,差异有统计学意义（P＜0.05,A=3.602;P＜0.05）.结论 HLA-DRB1＊0701与家族性慢性乙型肝炎易感性相关,可能是家族性慢性乙型肝炎的易感基因或连锁基因;HLA-DRB1＊0401/0403/0405、HLA-DRB1＊1301/1302与家族性慢性乙型肝炎抗性相关,可能是家族性慢性乙型肝炎的抗性基因.宿主的HLA-DRB1可能是预测家族性乙肝转归的主要指标.     

The influence of HLA alleles and HBV subgenotyes on the outcomes of HBV infections in Northeast China

Hepatitis B virus (HBV) infection has a wide variety of clinical outcomes, it could be spontaneouly recovered and also could develop fulminant liver failure or cirrhosis with hepatocellular carcinoma. Human leukocyte antigen (HLA) polymorphism and HBV (sub)genotypes have been speculated to associate with the outcome of HBV infection because the data obtained from various populations who bear different HLA alleles have shown a HLA polymorphism associated outcome of HBV infection. However, as the most important viral and host genetic factors, the impact of HBV (sub)genotypes in combination with HLA polymorphism on the clinical outcomes of HBV infections remains unclear. To demonstrate the association of HLA allele polymorphism in combination with HBV subgenotypes with the outcome of HBV infection in Northeastern Han Chinese population, a total of 230 HBV-infected individuals (Infection group) were compared to 210 random selected controls (Control group) who are negative for HBV infection for their HLA alleles frequency as well as the associations with the virus infection, clearance and persistence in combination with HBV subgenotypes. Of the 230 HBV-infected subjects, 54 were acute self-limited hepatitis (ASH) with HBV subgenotype C2 (ASH-C2), 144 were chronic hepatitis (CH) with HBV subgenotype C2 and B2 (CH-C2 and CH-B2), and 32 were spontaneously recovered (SR) without subgenotype results. When two groups are compared, the results suggest that B*48, B*51 and DRB1*12 carrier may have a high risk for HBV infection, but B*51 is likely association with spontaneous recovery and DRB1*07, 12 may be implied in viral persistence. HLA-B*15, DRB1*11 and 14 associated with viral clearance in the cases of HBV-C2 infection; HLA-B*54 carriers in chronic group are more sensitive to with the infection of HBV subgenotype B2; HLA-B*07 and DRB1*13 may protect subjects from HBV infection. The data presented a link between HLA polymorphism and HBV pathogenesis and suggested potential therapeutic targets for hepatitis B.     

Association of polymorphisms of human leucocyte antigen-DQA1 and DQB1 alleles with chronic hepatitis B virus infection, liver cirrhosis and hepatocellular carcinoma in Chinese

To investigate whether human leucocyte antigen (HLA) class II DQA1 and DQB1 gene polymorphisms are associated with chronic hepatitis B virus (HBV) infection and development of HBV-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC), we detected the DQA1 and DQB1 allele polymorphisms in 168 HBV carriers (including 48 chronic hepatitis B, 42 LC and 78 HCC patients) and 100 controls who had recovered from HBV infection by using polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). Our data suggest that DQA1*0102 and DQA1*0104 were associated with protection from chronic HBV infection (P(c) = 0.003) and development of LC (P(c) = 0.001), respectively, whereas DQB1*0201 conferred susceptible effect on chronic HBV infection (P(c) = 0.008). We also found that DQA1*0601, DQB1*0601 and DQA1*0201 showed some susceptible effect on chronic HBV infection and LC, respectively, however, these associations were no longer significant after Bonferroni correction (P(c) = 0.390, P(c) = 0.475 and P(c) = 0.140, respectively). No significant association has been found between DQA1 and DQB1 alleles and development of HCC. These results indicate that different subtypes of HLA-DQA1 and DQB1 are associated with development of chronic HBV infection and LC, respectively, in Han Chinese population.     

Association of HLA-DRB1*0901-DQB1*0303 haplotype with microscopic polyangiitis in Japanese

Microscopic polyangiitis (MPA) is a rare and severe form of systemic necrotizing vasculitis associated with myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA). We previously reported significant association of HLA-DRB1*0901 with MPA. To define the susceptibility loci within the HLA region, we determined the genotypes of HLA-DQB1, DPB1, B and C in 50 patients with MPA and 77 unrelated Japanese controls. In addition to HLA-DRB1*0901, significant association of DQB1*0303 (allele carrier frequencies 50% in MPA, 29.9% in controls, odds ratio 2.35, P = 0.017) was detected. These alleles were in strong linkage disequilibrium (D' = 0.95, r2 = 0.82). Increased frequency was also observed for DPB1*0201, B*15111 and Cw*0303, which was at least partly accounted for by linkage disequilibrium with DRB1*0901 and DQB1*0303. These results indicate that DRB1*0901-DQB1*0303 haplotype represents the primary genetic risk for MPA within the HLA region in Japanese, and provides the basis that future functional studies on the role of HLA in MPA should target DR9, DQ9 and DR53 proteins encoded by this haplotype.     

HLA-DQA1基因多态性与HBV感染结局相关

目的探讨中国汉族人群人类白细胞抗原(HLA)-DQA1基因多态性是否与乙型肝炎病毒(HBV)感染结局相关联。方法以213例HBV自限性感染者和420例慢性乙肝患者为研究对象,应用聚合酶链反应-序列特异性引物(PCR-SSP)技术进行HLA-DQA1基因分型,用EPI和SPSS软件分析DQA1多态性的分布频率及其组间差异。结果DQA1*0102在慢性乙肝组的分布频率显著低于HBV自限性感染组(15.47%比较20.42%,P<0.05),而DQA1*0201在慢性乙肝组的分布频率显著高于HBV自限性感染组(10.48%比较6.10%,P<0.05)。调整性别、年龄等混杂因素影响的非条件logistic回归分析结果显示,与HLA-DQA1其他等位基因相比,携带DQA1*0102者降低慢性乙肝发生的风险(P<0.05,OR=0.69,95%C I:0.49-0.96),而携带DQA1*0201者增加慢性乙肝发生的风险(P<0.05,OR=1.77,95%C I:1.09-2.87)。结论HLA-DQA1基因多态性可能是影响HBV感染结局的重要宿主遗传因素。     

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

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.     

Human leukocyte antigen class I and class II allele frequencies and HIV-1 infection associations in a Chinese cohort

China has one of the most rapidly spreading HIV-1 epidemics. To develop a vaccine targeted to specific human leukocyte antigen (HLA) epitopes in this population, allele distribution analysis is needed. We performed low-resolution class I and II HLA typing of a cohort of 393 subjects from mainland China using a polymerase chain reaction with sequence-specific primers (PCR-SSPs). We found 10 class I alleles present in more than 10% of the population: HLA-A*02, HLA-A*11, HLA-A*24, HLA-B*13, HLA-B*15, HLA-B*40, HLA-Cw*03, HLA-Cw*07, HLA-Cw*01, and HLA-Cw*06. Several class II alleles were found at high frequency (>or=10%): HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DRB1*0701, HLA-DRB1*1501, HLA-DRB1*0401, HLA-DRB1*0901, HLA-DRB1*1201, HLA-DQB1*0601, HLA-DQB1*0301, HLA-DQB1*0201, HLA-DQB1*0501, and HLA-DQB*0303. We also estimated 2- and 3-locus haplotype frequencies. Because this cohort contained 280 HIV-1-seropositive and 113 HIV-1-seronegative individuals, we compared allele and haplotype frequencies between the infected and control groups to explore correlations between HLA antigens and susceptibility/resistance to HIV infection. The HLA-B*14 allele was only found in the HIV-1-seropositive group, and many 2-locus haplotypes were significantly overrepresented in this group: HLA-B*14/Cw*08, HLA-B*51/Cw*14, HLA-A*02/B*13, HLA-A*31/Cw*14, HLA-A*02/Cw*06, and the class II haplotype HLA-DRB1*1301/DQB1*0601. Alleles significantly increased in the HIV-1-seronegative controls were HLA-B*44, HLA-Cw*04, and HLA-DRB1*1402. Overrepresented 2-locus haplotypes in the control group were HLA-B*44/Cw*04, HLA-A*31/Cw*03, HLA-A*03/Cw*07, HLA-A*11/B*13, HLA-A*11/B*38, HLA-A*24/B*52, and HLA-A*11/Cw*01. The 3-locus haplotypes HLA-A*24/Cw*03/B*40 and HLA-A*02/B*15/DRB1*1201 were found to be increased significantly in the control group. These data contribute to the database of allele frequencies and associations with HIV infection in the Chinese population.     

MHC class II alleles and haplotypes in patients with pemphigus vulgaris from India

Pemphigus vulgaris (PV) is a blistering disease of the skin and mucous membranes characterized by an autoantibody response against a keratinocyte adhesion molecule, desmoglein 3, causing acantholysis and blister formation. We compared high resolution MHC class II alleles and haplotype frequencies (HLA-DRB, DQA1 and DQB1) in 37 patients with PV to 89 haplotypes of normal relatives from New Delhi and Ahmedabad. We found that PV patients had significantly increased frequencies of DRB1*1404 (P<0.0001), DQA1*0101 (P=0.001), and DQB1*0503 (P<0.0001). These associations were due to the increased frequencies of the haplotype HLA-DRB 1 * 1404, DRB3*0202, DQA1*0101, DQB1*0503 in patients compared to control haplotypes (p<0.0001). Also, patients from Ahmedabad had a significant increase in HLA-DQB 1*0302 (p=0.03). An identical amino acid sequence (Leu-Leu-Glu-Arg-Arg-Arg-Ala-Glu), in positions 67–74 of the P domain of DRB alleles is restricted to some DR14 alleles. Therefore, there are three possible explanations for class II allele involvement in autoantibody in PV patients with class II haplotypes marked by HLA-DR14. First, the class II alleles could be markers for an unidentified susceptibility gene in linkage disequilibrium with them. Second, the primary association could be with DQB 1*0503 and the association with HLA-DR14 alleles would be the result of linkage disequilibrium. Third, the HLA-DRB 1 locus susceptibility could involve a specific amino acid sequence in the third hypervariable region shared by several HLA-DR14 alleles.     

Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans

Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) is occurring at high prevalence in most Asian endemic areas. There have been some reports on human leucocyte antigen (HLA) associations with HBV infections; however, HLA association with HBV-GN has been rarely reported. Forty-six adult Korean patients with HBV-GN (42 male and four female patients, age 20-66), 100 HBsAg (-) healthy controls, and 89 individuals with chronic HBV infection were studied for HLA-DRB1 and DQB1 gene polymorphisms using high-resolution DNA typing methods. In HBV-GN patients, a strong association with HLA-DR2 was observed compared with HBsAg (-) controls (OR = 4.0). Different HLA-DR2 alleles were associated with different pathologic subtypes of HBV-GN: DRB1*1502 with membranoproliferative glomerulonephritis (MPGN, n = 35) (OR = 14.5) and DRB1*1501 with membranous nephropathy (MN, n = 11) (OR = 3.8). HLA-DQB1*0601, strongly linked to DRB1*1502, was also associated with MPGN subtype of HBV-GN (OR = 4.3). All these associations were also significant compared with chronic HBV infection group. For chronic HBV infection per se, DRB1*1302, DQB1*0402, and DQB1*0604 had some protective effect (OR = 0.4, OR = 0.3, and OR = 0.1, respectively), and DRB1*1101 was weakly associated (OR = 4.6) in Koreans. These results suggest that HLA-DR or related genetic factor is associated with disease susceptibility to HBV-GN in Koreans, and different pathologic subtypes of HBV-GN are influenced by the genetic factors of the patients.     

吉林汉族人群乙型肝炎肝硬化患病与HLA-DRB1等位基因的关联性

目的：探讨吉林地区汉族人群乙型肝炎肝硬化患病与白细胞抗原（HLA）DRB1区等位基因多态性的关联性。方法：采用PCR-SSP方法对吉林地区汉族61例慢性乙型肝炎,44例乙型肝炎肝硬化患者,32名HBV感染自然恢复者及50名健康献血员作对照进行了HLA-DRB1等位基因分型比较。结果：慢性乙型肝炎组HLA-DRB1＊1201-3等位基因表达频率为17.21%,明显高于正常对照组8.00%（P=0.0427,RR=2.391）；慢性乙型肝炎组与乙型肝炎肝硬化组HLA-DRB1＊0701等位基因频率分别为11.48%,12.50%,明显高于正常对照组2.00%（P=0.0066,RR=6.35；P=0.0046,RR=7.00）及HBV感染自然恢复组1.56%（P=0.0183,RR=8.17；P=0.0136,RR=9.00）；而所检测HLA-DRB1座位的其它等位基因表达频率在四组间无显著性差异（P〉0.05）。结论：吉林地区汉族人群慢性乙型肝炎患病与HLA-DRB1＊1201-3、HLA-DRB1＊0701等位基因型相关联；而乙型肝炎肝硬化患病仅与HLA-DRB1＊0701等位基因型相关联。     

慢性乙型肝炎病毒感染与HLA-DRB1基因的相关性研究

目的： 研究HLA-DRB1等位基因与HBV感染慢性化的相关性。 方法： 用PCR-SSP 方法对陕西地区汉族乙肝患者108例与正常对照108人以及慢性乙型肝炎表面抗原携带者32人，进行HLA-DRB1等位基因分型比较，并进行HLA-DRB1等位基因分型与HBV不同复制状态相关性分析。 结果： 陕西地区汉族人HLA-DRB1等位基因以DRB1*04（16.2%），DRB1*09（12.5%），DRB1*12（11.6%）, DRB1*15（13.4%）最为常见；病例组HLA－DRB1*03 的等位基因频率(10.6%)明显高于健康对照组(3.7%)，(OR=3.10; P<0.05)；HLA-DRB1*07等位基因频率病例组(17.6%)明显高于健康对照组(9.3%)(OR=2.09; P<0.05)；DRB1*07 基因位点在HBV高复制状态多见（OR=2.22; P<0.05）; HLA-DRB1*15对照组等位基因频率13.4%, 明显高于病例组6.9% (OR=0.48; P<0.05)。 结论： HLA－DRB1*03、HLA-DRB1*07与陕西地区汉族人HBV感染后的慢性化相关联，HLA-DRB1*15为陕西地区汉族人乙肝感染的抗性基因。本研究提示HLA-Ⅱ类基因是决定HBV感染后临床转归的重要因素。     

HLA-DQB1等位基因多态性及Th1/Th2细胞相关因子与广西瑶族肝癌家族聚集性的相关性

目的：探讨HLA-DQB1等位基因多态性及相应位点下Th1/Th2细胞相关因子IL-2、IL-4及IL-10对广西瑶族原发性肝癌家族聚集性的影响,为寻找广西瑶族原发性肝癌的遗传易感基因或拮抗基因提供线索。方法：在广西肝癌高发区选取民族为瑶族的肝癌高发家族成员、无癌家族成员各40例作为研究对象（采用相同性别、年龄±5岁配对方法）,采集研究对象外周血并提取全血DNA,应用PCR-SSP的方法对HLA-DQB1等位基因进行检测,应用ELISA法检测IL-2、IL-4、IL-10的水平。结果：（1）广西瑶族肝癌高发家族组的HLA-DQB1*02/09等位基因表达频率高于无癌家族组,两组比较差异明显,具有统计学意义（P<0.05）;而两组间的HLA-DQB1*04/05/06/07/08等位基因表达频率无显著性差异（P>0.05）。（2）HLA-DQB1各等位基因在乙型肝炎病毒感染组（HBsAg阳性组）及非乙型肝炎病毒感染组（HBsAg阴性组）间的分布频率比较无显著性差异（P值均>0.05）。（3）广西瑶族肝癌高发家族成员组中Th2细胞相关因子IL-4、IL-10平均表达水平高于无癌家族成员组,差异具有统计学意义（P<0.05）,而两组间的IL-2浓度无显著性差异（P>0.05）。（4）两组中HLA-DQB1*02阳性成员的IL-10平均表达水平高于HLA-DQB1*02阴性成员,差异具有统计学意义（P<0.05）。（5）两组中HLA-DQB1*09阳性成员的IL-4平均表达水平高于HLA-DQB1*09阴性成员,差异具有统计学意义（P<0.05）。结论：（1）HLA-DQB1*02/09等位基因可能是广西瑶族居民原发性肝癌发生的易感基因。（2）HLA-DQB1各等位基因与广西瑶族居民的HBV感染可能无显著相关性。（3）IL-4、IL-10表达水平失衡可能是广西瑶族肝癌家族聚集性的危险因素。（4）IL-10表达水平失衡可能与HLA-DQB1*02等位基因的携带有关,而IL-4表达水平失衡可能与HLA-DQB1*09等位基因的携带有关,它们之间共同作用可能与广西瑶族肝癌家族聚集性的发生有相关性。