摘要
目的探讨人类白细胞抗原(human lymphoeyte antigen,HLA)-DRB1等位基因多态性与山西省家族性乙型肝炎临床转归及乙型肝炎病毒(HBV)复制状态的相关性。方法采用前瞻性临床流行病学研究方法,以山西省家族性乙型肝炎家庭中的295位成员为研究对象,将其分为健康对照组、慢性无症状携带(ASC)组、慢性乙型肝炎(CHB)组及肝硬化组。采用聚合酶链反应.序列特异性寡核苷酸探针技术(polymerase chain reaction—sequence specific oligonucleotide probe,PCR—SSOP)结合荧光磁珠流式检测技术,进行HLA—DRB1等位基因检测。采用,检验或Fisher’s确切概率计算法比较HLA—DRB1各等位基因频率在各组间以及在HBV DNA不同载量下的分布情况,组间计量资料比较采用方差分析,相关疾病的等位基因风险率以相对危险系数(RR)表示。结果HLA—DRB*04基因频率在健康对照组为0.159,明显高于ASC组(0.069)和CHB组(0.079),差异具有统计学意义(χ^2分别为4.892和4.072,P值均〈0.05);HLA—DRB1*07等位基因在CHB组和肝硬化组的频率分别为0.131和0.154,明显高于健康对照组(0.049),差异具有统计学意义(χ^2值分别为4.140和5.529,P值均〈0.05);HLA—DRB1*13等位基因频率在健康对照组为0.037,高于CHB组(0),2组比较差异具有统计学意义(χ^2=3.316,P〈0.05)。HLA—DRB1*15等位基因频率在ASC组为0.206,在肝硬化组为0.115,2组比较差异具有统计学意义(χ^2=4.287,P〈0.05)。其他各等位基因频率在各组间差异无统计学意义。患者年龄在ASC、CHB及肝硬化3组间的差异有统计学意义(F=33.38,P〈0.01);HBV DNA阳性组的HLA—DRB1*07基因频率(0.167)高于HBV DNA阴性组(0.096)(χ^2=5.268,P=0.002)。结论HLA—DRB1*07与家族性HBV易感性有关,可能是山西省家族性乙型肝炎易感基因或连锁基因。HLA—DRBI*04及HLA—DRB1*13与家族性乙型肝炎抗性相关,可能是山西省家族性乙型肝炎抗性基因。
Objective To assess the associations of human leukocyte antigen (HLA)-DRB1 polymorphism with the outcome of familial hepatitis B and the replication of hepatitis B virus ( HBV ) in Shanxi province. Methods A prospective clinical and epidemiological study was performed in 295 subjects from hepatitis B families who were divided into the healthy control group, chronic asymptomatic carrier (ASC) group, chronic hepatitis B (CHB) group and liver eirrhosis group. The frequencies of HLA-DRB1 were deteeted by polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) and fluorescence luminex flow technique. χ^2 test and Fisher's exact probability test were used to compare the frequencies of HLA-DRB1 among the groups and among different replications of HBV. Analysis of variance was performed to compare the measurement data among groups. The relative risks for HLA-DRB1 associated with other diseases were expressed in HR. Results The frequency of HLA-DRB1 * 04 in the healthy control was 0. 159, which was higher than those in CHB group (0. 069) and liver cirrhosis group (0. 079), and the differences were of statistical significance (χ^2 = 4. 892 and 4. 072, P 〈 0. 05 ). The frequencies of HLA- DRB1 * 07 in CHB group and liver cirrhosis group were 0. 131 and 0. 154, significantly higher than that in the healthy control (0.049, χ^2 =4. 140 and 5. 529, P 〈0.05). The frequency of HLA-DRB1 * 13 in the healthy control group was 0. 037, which was higher than that in the CHB group (0, χ^2 = 3. 316, P 〈 0.05). The frequencies of HLA-DRB1 * 15 in ASC group and liver cirrhosis group were 0. 206 and 0. 115, the difference between the two groups was of statistical significance (χ^2 = 4.287, P 〈 0.05 ). The frequencies of other DRB1 alleles were not significantly different among the groups. Significant difference on the average ages was observed among ASC, CHB and liver cirrhosis groups (F = 33.38, P 〈 0.01 ). The frequency of HLA- DRB1 * 07 was significantly higher in the HBV DNA positive group than that in the HBV DNA negative group (0. 167 vs. 0. 096, χ^2 = 5. 268, P = 0. 002). Conclusions HLA-DRB1 * 07 allele is associated with the susceptibility to familial hepatitis B, which may be the susceptibility gene or linked gene for familial hepatitis B in Shanxi province. HLA-DRB1 * 04 and HLA-DRB1 * 13 are associated with the resistance to familial hepatitis B, which may be the resistant genes for familial hepatitis B in Shanxi province.
出处
《中华临床感染病杂志》
CAS
2010年第1期40-43,共4页
Chinese Journal of Clinical Infectious Diseases
基金
山西省高校科技研究自筹项目(20091173)
关键词
肝炎
乙型
人类白细胞抗原
多态性
转归
Hepatitis B
Human leukocyte antigen
Polymorphism
Outcome