Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA.
Modification of Multiple Sclerosis Phenotypes by African Ancestry at HLA.
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DOI：
10.1001/archneurol.2008.541
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发表时间：
2009-02
影响因子：
--
通讯作者：
Oksenberg, Jorge R.
中科院分区：
文献类型：
--
作者：
Cree, Bruce A. C.;Reich, David E.;Khan, Omar;De Jager, Philip L.;Nakashima, Ichiro;Takahashi, Toshiyuki;Bar-Or, Amit;Tong, Christine;Hauser, Stephen L.;Oksenberg, Jorge R.
在那些患有多发性硬化症(MS)的人中，非裔美国人的病程更严重，发病年龄更大，临床表现更多地局限于视神经和脊髓(视脊髓MS)，而不是白人。以确定基因变异是否影响临床多发性硬化症的模式。多中心回顾性队列研究。对673名非裔美国人和717名白人MS患者进行了HLADRB1和HLADQB1等位基因分型。通过对已知在西非和欧洲人群中存在显著频率差异的单核苷酸多态进行基因分型，估计了人类白细胞抗原欧洲血统的比例。这些基因型别与视神经疾病表型、残疾程度和发病年龄相关。携带DRB1*15等位基因的受试者患典型多发性硬化症的可能性是视髓型多发性硬化症的两倍(P=.001)。在抗水通道蛋白4抗体血清阳性(约5%)的视神经脊髓型多发性硬化症或复发性横贯性脊髓炎患者中，没有人携带DRB1*15等位基因(P=0.008)。与DRB1*15无关，人类白细胞抗原非洲血统与多发性硬化症严重程度评分(P<；.001)和甘蔗依赖风险(风险比，1.36；P<；.001)测量的残疾相关；DRB1*15等位基因与发病年龄早2.1年相关(P<；.001)。这些数据表明，人类白细胞抗原在多发性硬化症中的作用不仅限于疾病易感性，而且嵌入该基因的基因也影响临床结果。
In those with multiple sclerosis (MS), African American individuals have a more severe disease course, an older age at onset, and more often have clinical manifestations restricted to the optic nerves and spinal cord (opticospinal MS) than white persons. To determine whether genetic variation influences clinical MS patterns. Retrospective multicenter cohort study. Six hundred seventy-three African American and 717 white patients with MS. Patients with MS were geno-typed for HLA-DRB1 and HLA-DQB1 alleles. The proportion of European ancestry at HLA was estimated by genotyping single-nucleotide polymorphisms with known significant frequency differences in West African and European populations. These genotypes were correlated with the opticospinal disease phenotype, disability measures, and age at onset. Subjects with DRB1*15 alleles were twice as likely to have typical MS rather than opticospinal MS (P = .001). Of the subjects with opticospinal MS or a history of recurrent transverse myelitis who were seropositive for anti–aquaporin 4 antibodies (approximately 5%), none carried DRB1*15 alleles (P = .008). Independently of DRB1* 15, African ancestry at HLA correlated with disability as measured by the Multiple Sclerosis Severity Score (P < .001) andriskof cane dependency (hazard ratio, 1.36; P < .001); DRB1*15 alleles were associated with a 2.1-year earlier age at onset (P < .001). These data indicate that the role of HLA in MS is not limited to disease susceptibility but that genes embedded in this locus also influence clinical outcomes.
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影响因子：
9.8
作者：
Barcellos, LF;Oksenberg, JR;Hauser, SL
通讯作者：
Hauser, SL
影响因子：
11.2
作者：
McDonald, WI;Compston, A;Wolinsky, JS
通讯作者：
Wolinsky, JS
影响因子：
9.9
作者：
Brassat, D;Azais-Vuillemin, C;Fontaine, B
通讯作者：
Fontaine, B
影响因子：
9.9
作者：
Roxburgh, RHSR;Seaman, SR;Compston, DAS
通讯作者：
Compston, DAS
影响因子：
9.9
作者：
Hensiek, A. E.;Seaman, S. R.;Compston, D. A. S.
通讯作者：
Compston, D. A. S.