儿童开始的系统性红斑狼 (cSLE) 的遗传学
Raffaella Carlomagno1,2, Nicholas Gold1, Fangming Liao1
1Division of Rheumatology, The Hospital for Sick Children, Toronto, Canada.
Arthritis & rheumatology (Hoboken, N.J.)
|May 13, 2025
概括
遗传变异影响全身性红斑狼 (SLE) 诊断年龄. 在CCDC113附近的一个新位与较早的SLE发作有关. 第一个童年发病的SLE GWAS发现了一个TSBP1-AS1位点.
科学领域:
- 遗传学 遗传学 是一个
- 免疫学 免疫学 免疫学
- 儿科 儿科 儿科
背景情况:
- 全基因组关联研究 (GWAS) 已经确定了100多个与系统性红斑狼 (SLE) 相关的位点.
- 这些已知的SLE风险位点也可能影响个体被诊断患有这种疾病的年龄.
- 了解影响SLE发病年龄的遗传因素对于早期诊断和管理至关重要.
研究的目的:
- 为了确定与SLE诊断年龄相关的遗传变异.
- 专门针对儿童发病性SLE (cSLE) 进行GWAS,定义为在18岁之前诊断.
- 调查已知的SLE位点在确定SLE诊断年龄方面的作用.
主要方法:
- 对1489名SLE患者的分析,诊断时的年龄有记录,在多民族阵列上进行基因型定型,并对未定型的SNP和HLA等位基因进行归算.
- 测试142个非HLA和166个HLA SLE风险位与SLE诊断的日志转换年龄的关联,调整性别和主要组件.
- 进行了GWAS,将346名cSLE患者与4080名欧洲和东亚血统的非SLE对照进行了比较.
主要成果:
- 在CCDC113中,显著的SLE风险SNP与SLE诊断的年轻年龄相关 (P=6.3x10−6) 和cSLE与成人发病SLE (aSLE).
- 在cSLE的第一个GWAS中,TSBP1-AS1在6号染色体上发现了一个显著的SNP (rs9268469) (P=1.79x10−8).
- 以前与aSLE相关的HLA-DQA1位点在cSLE GWAS中也被确定.
结论:
- 一个新的遗传位点,CCDC113,在多祖先队列中与SLE诊断的早期年龄显著相关.
- 对于cSLE的第一个GWAS已经确定了一个新的风险位置,TSBP1-AS1.1.
- 这些发现突出了对SLE发病时间和儿童疾病的特定风险因素的遗传贡献.
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