Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis
Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis
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DOI：
10.1111/j.0001-2815.2004.00173.x
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发表时间：
2004-03-01
期刊：
影响因子：
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通讯作者：
Spurkland, A
中科院分区：
文献类型：
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作者：
Harbo, HF;Lie, BA;Spurkland, A
为了分析人类白细胞抗原 (HLA) I 类区域中的基因座是否可能导致 HLA II 类相关的多发性硬化症 (MS) 遗传易感性，我们检查了 177 个北欧同胞对家庭、222 个英国同胞对家庭、323 名散发性挪威 MS 患者和 386 名挪威对照的选定微卫星标记。此外，所有样本均进行了 HLA-DR DQ 单倍型基因分型，挪威病例对照样本也进行了 HLA-A 和 -B 基因座分型。在挪威散发性多发性硬化症患者中，发现与 HLA-A、HLA-B 以及位于 HLA-A 着丝粒 100 kb 处的 D6S265 标记物存在关联。当将分析限制于 HLA-DR15 单倍型时，还提出了与 HLA-A 和 D6S265 位点的关联。在同胞对数据中，标记 D6S265 也出现了类似的趋势。与仅携带 HLA-DR15 (GRR = 7)、仅携带 HLA-A3 (GRR = 3) 或不携带这些等位基因 (GRR = 1) 的个体相比，同时携带 HLA-DR15 和 -A3 (GRR = 15) 的个体的基因型相对风险 (GRR) 更高。 HLA-DR15 和 -A3 的组合赋予最高风险（比值比 (OR) = 5.2）。这些结果表明 HLA-A 或与其连锁不平衡的基因可能与 HLA II 类相关的 MS 遗传易感性有关。
In order to analyze whether loci in the human leukocyte antigen (HLA) class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis (MS), we examined selected microsatellite markers in 177 Nordic sib-pair families, 222 British sib-pair families, 323 sporadic Norwegian MS patients and 386 Norwegian controls. All samples were, in addition, genotyped for the HLA-DR DQ haplotype, and the Norwegian case-control samples were also typed for HLA-A and -B loci. In the Norwegian sporadic MS patients association was seen with HLA-A, HLA-B, and with the D6S265 marker, located 100 kb centromeric to HLA-A. Associations with HLA-A and D6S265 loci were also suggested when restricting the analysis to HLA-DR15 haplotypes. In the sib-pair data a similar trend was seen with marker D6S265. Higher genotypic relative risk (GRR) was found for individuals who carry both HLA-DR15 and -A3 (GRR = 15), compared to those who carry only HLA-DR15 (GRR = 7), only HLA-A3 (GRR = 3) or none of these alleles (GRR = 1). The highest risk was conferred by a combination of HLA-DR15 and -A3 (odds ratio (OR) = 5.2). These results suggest that HLA-A or a gene in linkage disequilibrium with it may contribute to the HLA class II-associated genetic susceptibility to MS.