罕见和常见的单核酸变异在童年开始的全身性红血性狼中
Ahmed Sayadi1, Johanna K Sandling1, Maija-Leena Eloranta1
1Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.
Lupus science & medicine
|February 11, 2025
概括
罕见的有害变体在很少一部分儿童发病SLE (cSLE) 患者中被发现. 这些患者具有与健康个体相似的多基因风险评分 (PRS),突出显示了儿科SLE罕见变异的作用.
科学领域:
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
- 系统性自身免疫性疾病
背景情况:
- 系统性红斑狼 (SLE) 与许多常见的遗传风险变体有关.
- 罕见的基因变异也可能导致单基因形式的SLE.
- 在SLE病原体中常见和罕见的遗传变异之间的相互作用仍然不清楚.
研究的目的:
- 调查儿童发病性SLE (cSLE) 和成人发病性SLE (aSLE) 罕见有害变异的频率.
- 为了比较这些罕见变异的患病率与SLE多基因风险评分 (PRS).
主要方法:
- 针对1832个基因区域的定向测序,包括31个单一的SLE相关基因.
- 分析了958名SLE患者 (116名cSLE患者) 和1026名健康对照.
- 从37个单核酸变异 (SNV) 中计算SLE常见变异多基因风险评分 (PRS).
主要成果:
- 在23个单基性SLE相关基因中发现了罕见编码有害SNV (RD SNV).
- 在cSLE患者中有6%,aSLE患者中有4.6%,对照组中有3.2%,存在RD SNV.
- 在cSLE中,在包括C1S,DDX58,IFIH1,IKZF1,RNASEH2A和C8A在内的基因中发现了RD SNV.
- 患有这些变异的cSLE患者的平均PRS与对照组相似.
结论:
- RD SNVs存在于cSLE患者的一小部分人群中.
- 在cSLE中携带RD SNV的携带者表现出类似于健康个体的PRS.
- 在特定的儿科病例中,罕见的编码异合体变异可能会显著增加SLE风险.
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