Centre of Neuromuscular and Neurological Disorders, University of Western Australia, and Department of Neurology, Sir Charles Gairdner Hospital, Queen Elizabeth Medical Centre, Perth, Western Australia, Australia.
Mult Scler. 2010 May;16(5):526-32. doi: 10.1177/1352458510362997. Epub 2010 Mar 5.
Previous studies on the influence of HLA-DRB1 alleles on multiple sclerosis (MS) susceptibility and clinical course have mostly employed the 2-point genotyping method.
To assess the influence of HLA-DRB1 alleles and allele interactions on disease risk and clinical course in a large West Australian MS patient cohort using high-resolution genotyping.
Four digit HLA-DRB1 genotyping was performed on a group of 466 clinically definite or probable MS patients from the Perth Demyelinating Diseases Database and 189 healthy Caucasian controls from the Busselton Community Health Study.
In addition to the known risk allele HLA-DRB11501, evidence of increased susceptibility to MS was found for three additional alleles, DRB10405, DRB11104 and DRB11303, though the power was insufficient to sustain significance for these when crudely Bonferroni corrected over all alleles considered. DRB10701 was found to be protective even after correction for multiple comparisons. In addition we found evidence that the DRB104 sub-allele HLA-DRB10407 and HLA-DRB10901 may be protective. Among the diplotypes, the highest estimated risk was in HLA-DRB11501/0801 heterozygotes and DRB11501 homozygotes and the lowest in HLA-DRB10701/0101 heterozygotes. There was no significant gender association with HLA-DRB11501 overall, but the HLA-DRB1*1501/1104 risk genotype was significantly associated with female gender. HLA-DRB11501 was the strongest risk allele in both primary progressive MS and relapsing-remitting MS.
Our results demonstrate the advantages of high-resolution HLA genotyping in recognizing risk-modifying alleles and allele combinations in this patient cohort and in recognizing the differential effects of HLA-DRB104 and DRB111 sub-alleles.
先前关于 HLA-DRB1 等位基因对多发性硬化症（MS）易感性和临床病程影响的研究大多采用两点基因分型方法。
使用高分辨率基因分型评估 HLA-DRB1 等位基因和等位基因相互作用对西澳大利亚州大型 MS 患者队列中疾病风险和临床病程的影响。
对来自珀斯脱髓鞘疾病数据库的 466 例临床确诊或可能的 MS 患者和来自巴斯顿社区健康研究的 189 名健康白种人对照者进行了四位数字 HLA-DRB1 基因分型。
除了已知的风险等位基因 HLA-DRB11501 外，还发现了三个额外的等位基因，即 DRB10405、DRB11104 和 DRB11303，对 MS 易感性增加，尽管在对所有考虑的等位基因进行粗糙的 Bonferroni 校正后，这些结果的效力不足以维持其显著性。即使在进行多次比较校正后，也发现 DRB10701 具有保护作用。此外，我们还发现证据表明，DRB104 亚等位基因 HLA-DRB10407 和 HLA-DRB10901 可能具有保护作用。在单体型中，估计风险最高的是 HLA-DRB11501/0801 杂合子和 DRB11501 纯合子，最低的是 HLA-DRB10701/0101 杂合子。总体而言，HLA-DRB11501 与性别无显著关联，但 HLA-DRB1*1501/1104 风险基因型与女性显著相关。在原发性进展性 MS 和复发缓解性 MS 中，HLA-DRB11501 均为最强的风险等位基因。
我们的结果表明，高分辨率 HLA 基因分型在识别该患者队列中的风险修饰等位基因和等位基因组合以及识别 HLA-DRB104 和 DRB111 亚等位基因的差异效应方面具有优势。
