The rs10191329 Risk Allele Is Associated With Pronounced Retinal Layer Atrophy in Multiple Sclerosis.

IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY
Gabriel Bsteh, Ruchi Tanavade, Nik Krajnc, Fabian Föttinger, Theresa König, Martin Krenn, Lukas Haider, Barbara Kornek, Fritz Leutmezer, Kerstin U Ludwig, Stefan Macher, Tobias Monschein, Markus Ponleitner, Paulus Rommer, Christiane Schmied, Karin Zebenholzer, Tobias Zrzavy, Gudrun Zulehner, Franziska Di Pauli, Axel Schmidt, Harald Hegen, Berthold Pemp, Thomas Berger
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引用次数: 0

Abstract

Objective: To investigate whether the rs10191329 risk allele in the DYSF-ZNF638 locus, which is implicated in central nervous system resilience rather than immune-mediated pathology, is associated with retinal layer thinning, a biomarker of neuroaxonal damage in relapsing multiple sclerosis (RMS).

Methods: From a prospective observational study, we included RMS patients with ≥ 2 optical coherence tomography (OCT) scans, excluding eyes with optic neuritis during the observation period. DNA samples were genotyped using the Illumina Infinium Global Screening Array-24 and variants imputed using the Haplotype Reference Consortium panel and Minimac4. Multivariable linear regression models were used to assess the association between rs10191329 risk allele number (rs10191329*A) and annualized rates of peripapillary retinal nerve fiber layer (aLpRNFL) and macular ganglion-cell-and-inner-plexiform-layer (aLGCIPL) atrophy, adjusting for age, sex, MS-specific variables, and 10 ancestry components.

Results: We included 183 RMS patients (mean age 35.9 years [SD 9.6], 74.9% female, median EDSS 2.0 [range 0-6.5], median observation 25 months [12-73], median OCT scans 3 [2-5]). Multivariable analyses revealed that each rs10191329*A allele was associated with a 0.10%/year increase in aLpRNFL (95% confidence interval [CI] 0.05-0.19, p < 0.001) and a 0.11%/year increase in aLGCIPL (95% CI 0.07-0.19, p < 0.001). The rs10191329 variant explained 8.9% of GCIPL atrophy and 8.2% of pRNFL atrophy variance.

Interpretation: Carriers of the rs10191329 risk allele show accelerated retinal atrophy, suggesting heightened neuroaxonal vulnerability in MS. While clinical implications are currently unclear, genetic stratification may be reasonable in clinical trials targeting neuroprotection.

rs10191329风险等位基因与多发性硬化症患者视网膜层明显萎缩有关
目的:研究DYSF-ZNF638基因座中的rs10191329风险等位基因是否与视网膜层变薄有关,视网膜层变薄是复发性多发性硬化症(RMS)神经轴突损伤的生物标志物。DYSF-ZNF638基因座与中枢神经系统恢复能力有关,而不是免疫介导的病理。方法:通过前瞻性观察研究,我们纳入了具有2次以上光学相干断层扫描(OCT)的RMS患者,在观察期间排除视神经炎的眼睛。DNA样本使用Illumina Infinium Global Screening Array-24进行基因分型,使用Haplotype Reference Consortium panel和Minimac4进行变异输入。采用多变量线性回归模型评估rs10191329风险等位基因数(rs10191329*A)与乳头周围视网膜神经纤维层(aLpRNFL)和黄斑神经节细胞-内丛层(aLGCIPL)萎缩的年化率之间的关系,调整年龄、性别、ms特异性变量和10个祖先成分。结果:我们纳入183例RMS患者(平均年龄35.9岁[SD 9.6],女性74.9%,中位EDSS 2.0[范围0-6.5],中位观察25个月[12-73],中位OCT扫描3次[2-5])。多变量分析显示,每个rs10191329*A等位基因与aLpRNFL每年增加0.10%相关(95%置信区间[CI] 0.05-0.19, p)。解释:rs10191329风险等位基因的携带者视网膜萎缩加速,提示ms神经轴突易感性增高。
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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
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