首页|福建地区汉族人乙型肝炎肝硬化与人类白细胞抗原I类基因的相关性

福建地区汉族人乙型肝炎肝硬化与人类白细胞抗原I类基因的相关性

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目的:研究人白细胞抗原(HLA)-A基因多态性与福建地区汉族人乙型肝炎肝硬化的遗传易感性关系. 方法:以93例福建地区汉族人群乙型肝炎肝硬化患者(病例组)为研究对象,以同一地区84例健康人为对照人群(对照组),采用DNA测序分型技术(SBT)对HLA.A等位基因精确分型,计算各组等位基凶频率.对对照人群等位基因分布进行Hardy-Weinberg遗传平衡检验,应用遗传统计方法进行关联分析,确定与乙型肝炎肝硬化相关的易感基因及基因型. 结果:HLA-A等位基因差异显著性检验:病例组A*24(20.33%us9.52%,X2=7.938,P=0.005),A*2402(19.23%us8.33%,X2=7.212,P=0.009)和A*01(5.49%us 1.19%,X2=4.878,P=0.027),A*0101(4.95% us 0.60%,X2=5.955,P=0.015)等位基因频率明显高于对照组.病例组A * 33(3.85% us9.52%,X2=4.587,P=0.032),A*3303(4.40%us 9.52%,X2=4.440,P=0.032)基因频率也低于对照组.等位基因多因素分析:HLA-A*24主型(OR=2.397,95%CI:1.206~4.766,P=0.0126)和A * 2402亚型(OR=2.685,95%CI:1.306~5.521,P=0.0072)在病例组与对照组之间分布差异具有显著性.基因型多因素分析:A 2402(OR=3.254,95%CI:1.320~8.021,X2=6.5703,P=0.0104)和A0201(OR=2.411,95%CI:1.147~5.068,X2=5.399,P=0.0203)在病例组与对照组之间的差异也具有显著性.基因型剂量-效应关系分析:乙型肝炎肝硬化与HLA-A2402基因型剂量线性相关(OR=2.020,95%CI:1.095~3.728,X2=5.0624,P=0.0244). 结论:HLA-A * 2402等位基因及其基因型与乙型肝炎肝硬化存在阳性关联,可能足慢性乙型肝炎病毒感染肝硬化形成的易感基因.
HLA-A gene polymorphism in Fujian Han population with HBV-induced liver cirrhosis
AIM: To investigate the association between HLA-A gene polymorphism and the genetic susceptibility to HBV-induced liver cirrhosis in Fujian Han population. METHODS: Genotyping of HLA-A gene was performed in 93 patients with HBV-induced cirrhosis and 84 healthy individuals by SBT (Sequencing-Based Typing). The distribution of alleles in control group was checked by Hardy-Weinberg genetic equilibrium and the association between the disease and the frequencies of alleles was analyzed by genetic statistical methods to find out the gene polymorphisms contributing to the susceptibility of liver cirrhosis. RESULTS: The frequencies of alleles in A * 24 (20.33% vs 9.52%, χ2 = 7.938, P = 0.005), A * 2402(19.23% vs 8.33%, χ2 =7.212, P = 0.009), A*01 (5.49% vs 1.19%, χ2 = 4.878, P = 0.027) and A* 0101 (4.95% vs 0.60%, χ2 = 5.955, P = 0.015) in patient group were significantly higher than those in control group. However, the frequencies of A * 33 (3.85% vs 9.52%, χ2 = 4.587, P = 0.032) and A* 3303 (4.40% vs 9.52%, χ2 = 4.440, P = 0.032) alleles in patient group were significantly lower than those in control group. Multivariate analysis of alleles showed that significant distributional differences in HLA-A * 24prime type(OR = 2.397, 95% CI: 1.206-4.766, P = 0.0126) and A * 2402 subtype(OR = 2.411, 95%CI: 1.147-5.068, χ2 = 5.399, P = 0.0203) between the disease group and the control group. Multivariate analysis of genotypes showed significant difference in HLA-A 2402(OR=3.254, 95%CI: 1.320-8.021, χ2 = 6.5703, P = 0.0104) and A0201 (OR = 2.411, 95% CI: 1.147-5.068, χ2 = 5.399, P = 0.0203) between the disease groups and the control group. A significant dose-response relationship was observed between HBV infection induced liver cirrhosis and the genotype of HLA-A 2402 (OR = 2.020, 95% CI: 1.095 - 3.728, χ2 = 5.0624, P = 0.0244). CONCLUSION: HLA-A * 2402 allele and its genotype may play an important role as a genetic risk factor in the pathophysiology and development of HBV infection induced liver cirrhosis.

hepatitis Bliver cirrhosisHLAgene frequencygenotyping

李东良、郑建勇、彭经宙、赵书民、杨才生、林小钦、程变巧

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南京军区福州总医院肝胆内科,福建,福州,50025

第四军医大学西京消化病医院,陕西,西安,710033

第二军医大学长征医院感染科,上海200003

乙型肝炎 肝硬化 人类白细胞抗原 基因频率 基因分型

福建省自然科学基金

2006J0120

2009

第四军医大学学报
第四军医大学

第四军医大学学报

CSTPCDCSCD北大核心
影响因子:0.599
ISSN:1000-2790
年,卷(期):2009.30(18)
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