中国华北地区人群TAP1基因多态性与乙肝关联性的研究  

The association of TAP1 gene polymorphism and hepatitis B in population of north china

作　　者：李坤[1] 戴悦[2] 阴秀丽[3] 綦素霞[1] 宁涛[4] 曹邦伟[4] 徐昌青[5] 

机构地区：[1]山东大学医学院,济南250012 [2]北京大学第一附属医院输血科 [3]山东省荣军总医院 [4]北京市肿瘤防治研究所遗传室 [5]山东省千佛山医院

出　　处：《胃肠病学和肝病学杂志》2005年第1期66-70,共5页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的　探讨华北地区人群TAP1基因SNPs与乙肝发生的关联。方法　提取中国华北地区 176例乙肝患者及该地区2 0 8例健康献血者外周血基因组DNA ,用PCR方法扩增TAP1基因包含Codon3 3 3、63 7片段 ,采用DNA直接测序法检测健康个体基因型 ,用RFLP明确乙肝患者基因型。并采用PHASE1 0软件构建这两个多态性位点的个体单倍体型。以非条件Logistic回归校正混杂因素 ,并进行多态性与乙肝风险关联性的统计学分析。结果　TAP1基因 2个多态性位点在华北地区人群中具有多态性 (均为A→G)。其中Codon63 7多态性位点在两组人群中的差异有高度显著性 (P <0 . 0 1) ,较之野生型A/A ,杂合型A/GOR =4 . 68(95 %CI =2 . 99～ 7 . 3 3 ) ,纯合型G/GOR =6 . 3 4(95 %CI =2 . 49～ 16 . 13 ) ;Codon3 3 3多态性位点在两组人群中无差异 (P >0 . 0 5 )。在这两个位点所构建的单倍体型中 ,我们研究发现含有AG单倍体的个体在两组人群中具有高度差异 (P <0 . 0 1) ,OR =19 . 85 (95 %CI =8 . 3 3～47 . 3 1)。结论　TAP1基因Codon63 7位点的多态性对于乙肝的发生有着显著的易患关联 ,其杂合、纯合形式分别增加乙肝患病风险4 . 68倍和 6 . 3 4倍。而具有AG单倍体的个体对于乙肝的发生具有更强的易感关联 。Objective To investigate the association between the single nucleotide polymorphisms (SNPs) of transporter associated with antigen processing gene 1 (TAP1) and the susceptibility of hepatitis B in north Chinese.Methods Genomic DNA of 176 hepatitis B patients and 208 healthy controls were extracted from the peripheral blood leukocytes. Then two fragments covering Codon 333 and Codon 637 of the TAP1 gene were amplified by polymerase chain reaction (PCR). The SNPs of patients was revealed by restriction fragment length polymorphism (RFLP).Software PHASE 1.0 was used to construct the haplotypes of every individual. Unconditional logistic regression model was used to analyze the statistical association of genotypes or haplotypes in two groups adjusted by gender and age.Results There were significant differences in the SNPs of Codon 637 between the healthy control and hepatitis B patients in north China(P<0.01). Similarly, the combination of --/AG had a significant difference in two groups(P<0.01).Conclusion SNPs at Codon 637 of the TAP1 gene may relate to the susceptibility of hepatitis B, and the risk of hepatitis B in participants with G/G allele is 6.34 fold compared with those with A/A allele.Compared with other haplotypes, --/AG can accelerate the risk of hepatitis B 19.85 fold. These findings suggest that SNPs of TAP1 gene is one of the important host factors which independently influence the occurrence of hepatitis B.

关 键 词：乙肝患者 人群 TAP1 多态性位点 基因多态性 杂合 健康 基因组DNA 体型 SNP 

分 类 号：R512.62[医药卫生—内科学] R692[医药卫生—临床医学]