Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2
Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2
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1 型和 2 型自身免疫性肝炎易感性的遗传异质性
DOI：
10.1111/j.1572-0241.1999.01229.x
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发表时间：
1999
影响因子：
9.8
通讯作者：
J. Kalil
中科院分区：
文献类型：
--
作者：
P. Bittencourt;A. Goldberg;E. Cançado;G. Porta;F. Carrilho;A. Farias;S. A. Palácios;J. Chiarella;C. P. Abrantes;V. Baggio;A. Laudanna;J. Kalil
结论：1型自身免疫性肝炎（AIH）的易感性在欧洲和北美白人中与DRB 1 *03、DRB 1 *04和DRB 3等位基因相关，在日本与DRB 1 *04相关，在拉丁美洲与DRB 1 *04和DRB 1 *13相关。很少有关于AIH 2型的研究。方法：采用序列特异性引物聚合酶链反应扩增（PCR-SSP）技术对139例AIH患者进行HLA-DRB和-DQB 1基因分型。大多数AIH 1型与循环抗平滑肌抗体（F-actin特异性）或抗核抗体相关。结果：我们观察到AIH 1型患者DRB 1 *13（70%vs 26%，p < 0.00001）和DRB 3（93%vs 69%，p < 0.00001）显著增加。对无DRB 1 *13的患者的分析揭示了与DRB 1 *03的继发相关性（70%vs30%，p= 0.0001），大多数患者存在DRB 1 *13或DRB 1 *03等位基因（91%vs48%，p= 0.001）。DRB 1 *13和DRB 1 *03阳性受试者的比较显示，前者的等位基因赋予年轻的AIH 1型患者易感性。DQB 1分型显示DQB 1 *06显著增加（68%vs 41%的对照组，p= 0.00007），与DRB 1 *13存在强连锁不平衡，而DQB 1 *0301降低（8%vs 47%的对照组，pc= 0.0003）。另一方面，AIH 2型患者的HLA分型显示DRB 1 *07（68%vs20%，pc < 0.00014）、DRB 4（79%vs43%，pc= 0.004）和DQB 1 *02（86%vs42%，p= 0.00002）等位基因显著增加。在排除DRB 1 *07后，进一步观察到这些患者与HLA-DRB 1 *03的继发相关性（78%vs 30%，p= 0.007），大多数患者的DRB为1 *07或1 *03（93%vs 44%的对照组，pc < 0.0001）。我们的数据表明，AIH 1型和2型的易感性分别与DRB 1 *13或DRB 1 *03和DRB 1 *07或DRB 1 *03等位基因相关，并表明DQB 1 *0301可能具有针对1型疾病的保护作用。此外，DRB 1 *13在AIH 1型儿童中的聚集也支持不同HLA等位基因可能影响疾病发病的概念。
OBJECTIVES:Susceptibility to autoimmune hepatitis (AIH) type 1 has been associated with DRB1*03, DRB1*04, and DRB3 alleles in European and North-American whites, with DRB1*04 in Japan, and with DRB1*04 and DRB1*13 in Latin America. Very few studies have been performed on AIH type 2. The aim of the present study was to evaluate the association of AIH types 1 and 2 with HLA-DR and DQ loci.METHODS:We performed HLA-DRB and -DQB1 typing by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) in 139 AIH patients. Most had AIH type 1 associated with circulating anti-smooth muscle antibody with F-actin specificity or antinuclear antibody. Twenty-eight patients presented AIH type 2 with anti-liver/kidney microsome type 1 or anti-liver cytosol type 1 antibodies.RESULTS:We observed a significant increase of DRB1*13 (70%vs 26% of controls, p < 0.00001) and DRB3 (93%vs 69% of controls, p < 0.00001) in AIH type 1 patients. Analysis of patients without DRB1*13 disclosed a secondary association with DRB1*03 (70%vs 30% of controls, p= 0.0001) and either the DRB1*13 or the DRB1*03 alleles were present in the majority of these patients (91%vs 48% of controls, p= 0.001). Comparison of DRB1*13- and DRB1*03-positive subjects revealed that the former alleles conferred susceptibility to younger patients with AIH type 1. DQB1 typing showed a significant increase in DQB1*06 (68%vs 41% of controls, p= 0.00007) in strong linkage disequilibrium with DRB1*13, and a decrease in DQB1*0301 (8%vs 47% of controls, pc= 0.0003). On the other hand, HLA typing of patients with AIH type 2 disclosed a significant increase in the DRB1*07 (68%vs 20% of controls, pc < 0.00014), DRB4 (79%vs 43% of controls, pc= 0.004), and DQB1*02 (86%vs 42%, p= 0.00002) alleles. After exclusion of DRB1*07, a secondary association with HLA-DRB1*03 was further observed in these patients (78%vs 30%, p= 0.007) and most of them had either DRB1*07 or DRB1*03 (93%vs 44% of controls, pc < 0.0001).CONCLUSIONS:Our data indicate that predisposition to AIH types 1 and 2 is associated, respectively, with the DRB1*13 or DRB1*03 and DRB1*07 or DRB1*03 alleles, and suggest that protection against type 1 disease may be conferred by DQB1*0301. In addition, the cluster of DRB1*13 in children with AIH type 1 also supports the concept that different HLA alleles might influence the onset of the disease.
影响因子：
15.9
作者：
MANNS, MP;GRIFFIN, KJ;JOHNSON, EF
通讯作者：
JOHNSON, EF
自身免疫性慢性活动性肝炎的免疫遗传学研究：HLA、免疫球蛋白同种异型和自身抗体。
DOI：
10.1002/hep.1840070621
发表时间：
1987
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Krawitt,EL;Kilby,AE;Albertini,RJ;Schanfield,MS;Chastenay,BF;Harper,PC;Mickey,RM;McAuliffe,TL
通讯作者：
McAuliffe,TL