Howard Florey Institute, Melbourne, Australia.
PLoS One. 2010 Apr 2;5(4):e10003. doi: 10.1371/journal.pone.0010003.
Recent association studies in multiple sclerosis (MS) have identified and replicated several single nucleotide polymorphism (SNP) susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13-14 in addition to the well established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity, as demonstrated previously for the MS risk allele HLA-DR15. We investigated this hypothesis in a cohort of 1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towards association between the RPL5 risk SNP and time between first demyelinating event and relapse, and between the CD40 risk SNP and symbol digit test score. No associations were significant after correction for multiple testing. We found no evidence for the hypothesis that these new MS disease risk-associated SNPs influence disease severity.
最近的多发性硬化症（MS）关联研究已经确定并复制了多个单核苷酸多态性（SNP）易感位点，包括 CLEC16A、IL2RA、IL7R、RPL5、CD58、CD40 和染色体 12q13-14，除了已经确立的等位基因 HLA-DR15 之外。这些遗传易感性因素也有可能调节 MS 疾病的严重程度，正如先前对 MS 风险等位基因 HLA-DR15 的研究所示。我们在来自澳大利亚东南部的 1006 名特征明确的 MS 患者队列中研究了这一假设。我们测试了与疾病严重程度相关的 MS 相关 SNP，其中包括残疾、发病年龄、认知和脑萎缩。我们观察到 RPL5 风险 SNP 与首次脱髓鞘事件与复发之间的时间以及 CD40 风险 SNP 与符号数字测试评分之间存在关联的趋势。经过多次测试校正后，没有关联具有统计学意义。我们没有发现这些新的 MS 疾病风险相关 SNP 影响疾病严重程度的假设的证据。
