HLA class II susceptibility to multiple sclerosis among Ashkenazi and non-Ashkenazi Jews
HLA class II susceptibility to multiple sclerosis among Ashkenazi and non-Ashkenazi Jews
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DOI：
10.1001/archneur.56.5.555
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发表时间：
1999-05-01
影响因子：
--
通讯作者：
Karussis, D
中科院分区：
文献类型：
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作者：
Kwon, OJ;Karni, A;Karussis, D
目的：寻找以色列犹太人群中与多发性硬化症（MS）易感性相关的HLA II类等位基因和单倍型。设计：对临床明确的多发性硬化症患者进行为期7年的前瞻性研究。地点：以色列大耶路撒冷地区一所大学医院的神经病学诊所转诊中心。患者：来自以色列2个主要犹太民族共162例临床明确的多发性硬化症患者：104名德系犹太人（80名复发缓解或继发性进展，24名原发性慢性进展）和58名非德系犹太人（36名复发缓解或继发性进展，22名原发性慢性进展），与132名德系犹太人和120名非德系犹太人健康对照。主要结局指标：通过聚合酶链反应和序列特异性寡核苷酸探针杂交确定的各种HLA II类等位基因和单倍型与德系犹太人和非德系犹太人群体之间以及不同临床病程的关系。结果：在德系和非德系患者中均发现DRB1*1501、DQA1*0102、DQB1*0602单倍型与MS相关（P < 0.001和P = 0.04）。在非德系患者中，检测到DRB1*1303、DQA1*05和DQB1*0301单倍型与MS的新关联（P = .03）。MS易感等位基因DRB1*1501、DQA1*0102、DQB1*0602与德系犹太人患者相关（P < 0.001、P = 0.02、P = 0.01）；DRB1*1501和DRB1*1303在非德系患者中更为常见（P = 0.03, P = 0.04）。将患者再划分为临床亚组，DRB1*0801、DQA1*0102、DQA1*0401和DQB1*0602与德系犹太人患者原发性慢性进展性MS的相关性显著（分别为P = 0.03、P = 0.04、P = 0.04和P = 0.05），而DRB1*1501、DRB1*03011和DQBI*0602与非德系犹太人患者复发缓解或继发性进展相关（分别为P = 0.05、P = 0.05和P = 0.03）。结论：与以往的研究不同，这项研究首次显示了犹太人HLA II类等位基因与多发性硬化症之间的显著关联。与hla - dr2相关的单倍型的关联与非犹太白人MS患者相似，此外，我们的数据支持DRB1*1501是导致犹太人群中这种单倍型与MS之间关联的易感等位基因的可能性。我们的研究还强调了德系犹太人和非德系犹太人患者之间以及不同临床病程之间的HLA谱差异。后者可能表明MS的临床病程受遗传背景的影响。
Objective: To look for HLA class II alleles and haplo-types conferring susceptibility to multiple sclerosis (MS) in the Jewish population of Israel.Design: Population-based cohort of clinically definite patients with MS tested prospectively over 7 years.Setting: Referral center in a neurology clinic at a university hospital in the greater Jerusalem area in Israel.Patients: A total of 162 consecutive patients with clinically definite MS from the 2 main ethnic Jewish groups in Israel: 104 Ashkenazi (80 with a relapsing remitting or secondary progressive and 24 with a primary chronic progressive course of the disease) and 58 non-Ashkenazi (36 with a relapsing remitting or secondary progressive course and 22 with a primary chronic progressive course of the disease), matched with 132 Ashkenazi and 120 non-Ashkenazi healthy controls.Main Outcome Measures: The relationship between the various HLA class II alleles and haplotypes and MS, as defined by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization, among the Ashkenazi and the non-Ashkenazi Jewish sections and with respect to the different clinical courses of the disease.Results: The haplotype DRB1*1501, DQA1*0102, DQB1*0602 was found to be associated with MS among both Ashkenazi and non-Ashkenazi patients (P < .001 and P = .04, respectively). Among the non-Ashkenazi patients, a new association of haplotypes DRB1*1303, DQA1*05, and DQB1*0301 with MS was detected (P = .03). The MS susceptibility alleles, DRB1*1501, DQA1*0102, and DQB1*0602,were found in association with the Ashkenazi patients (P < .001, P = .02, and P = .01, respectively); DRB1*1501 and DRB1*1303 were more frequently observed among the non-Ashkenazi patients (P = .03, P = .04, respectively). On subdivision of the patients into clinical subgroups, associations of DRB1*0801, DQA1*0102, DQA1*0401, and DQB1*0602 with primary chronic progressive MS among the Ashkenazi patients were evident (P = .03, P = .04, P = .04 and P = .05, respectively), whereas DRB1*1501, DRB1*03011, and DQBI*0602 were associated with relapsing remitting or secondary progressive among the non-Ashkenazi patients (P = .05, P = .05, and P = .03, respectively).Conclusions: This study, unlike previous ones, is the first to show a significant association between HLA class II alleles and MS in the Jewish population. The association with the HLA-DR2-related haplotype is similar to that among non-Jewish white patients viith MS. Moreover, our data support the possibility that DRB1*1501 is the susceptibility allele responsible for the association between this haplotype and MS in the Jewish population. Our study also underscores differences in HLA profiles between Ashkenazi and non-Ashkenazi patients, and between the different clinical courses of the disease. The latter may indicate that the clinical courses of MS are influenced by the genetic background.