Department of Neurology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam UMC, P.O. Box 22660, Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.
Clin Rheumatol. 2021 Sep;40(9):3735-3743. doi: 10.1007/s10067-021-05684-w. Epub 2021 Apr 27.
We studied genetic risk factors associated with sarcoidosis within a family with a high prevalence of this disease.
We studied 41 members of a family with a high rate of sarcoidosis, including an index patient with treatment-resistant neurosarcoidosis. Whole genome sequencing was performed for six affected family members and variations associated with loss of function were filtered out as candidate genes. Findings were validated by using amplicon sequencing within all 41 family members with DNA available and candidate genes were screened on absence and presence within the sarcoidosis affected and non-affected.
Family members (n = 61) from 5 generations were available for participation including 13 subjects diagnosed with sarcoidosis (20%). Analyses identified 36 candidate variants within 34 candidate genes. Variations within three of these genes (JAK2, BACH2, and NCF1) previously have been associated with autoimmune diseases.
We identified 34 genes with a possible role in the etiology of sarcoidosis, including JAK2. Our results may suggest evaluation of JAK inhibitors in treatment-resistant sarcoidosis. Key Points • JAK2 has a potential role in the etiology of sarcoidosis and is a potential therapeutic target. • We identified 33 additional candidate genes of which BACH2 and NCF1 have been previously associated with autoimmune disease.
我们研究了一个高发家族中与结节病相关的遗传风险因素。
我们研究了一个高发结节病家族的 41 名成员，包括一名患有治疗抵抗性神经结节病的索引患者。对 6 名受影响的家族成员进行全基因组测序，并筛选出与功能丧失相关的变异作为候选基因。通过对所有 41 名有 DNA 可用的家族成员进行扩增子测序验证发现，并在受影响和未受影响的结节病患者中筛选候选基因。
来自 5 代的 61 名家族成员可参与研究，其中 13 名被诊断患有结节病（20%）。分析确定了 34 个候选基因中的 36 个候选变异。这些基因中的三个（JAK2、BACH2 和 NCF1）的变异以前与自身免疫性疾病有关。
我们确定了 34 个可能在结节病发病机制中起作用的基因，包括 JAK2。我们的结果可能表明在治疗抵抗性结节病中评估 JAK 抑制剂的作用。
JAK2 在结节病的发病机制中具有潜在作用，是一个潜在的治疗靶点。
我们还确定了 33 个其他候选基因，其中 BACH2 和 NCF1 以前与自身免疫性疾病有关。
