Ectopic co-expression of canonical and LINE1 and THE1A-exonizing IL23R transcripts in sarcoid myopathy

IF 2.3 3区生物学 Q2 GENETICS & HEREDITY

Journal of Human Genetics Pub Date : 2026-01-13 DOI:10.1038/s10038-025-01451-w

Aritoshi Iida, Shunsuke Funaguma, Ichizo Nishino

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Abstract

Sarcoidosis is a heterogenous inflammatory disease with complex genetic susceptibilities. Multi-ethnic genome-wide association studies have validated the association of sarcoidosis susceptibilities with single nucleotide variants on interleukin 23 receptor gene (IL23R), which is highly expressed in adrenal gland and testis, but not in skeletal muscle. Here we report concomitant ectopic expression of a canonical IL23R transcript and alternative polyadenylation of intron 6 of IL23R, leading to novel aberrant transcripts containing two retrotransposons, LINE1 (L1PA16) and THE1A, in the 3’ untranslated region (IL23RL1-THE1A), in sarcoid myopathy (SM) compared with non-SM disease controls. RT-qPCR confirmed the expression of both transcripts in an additional sample set, including 14 SM and 29 non-SM. We also observed expression of both transcripts in T cells by single-nucleus RNA-sequencing. These findings should serve as an additional resource for investigating the role of IL23R transcript variants in the genetic background of sarcoidosis susceptibility and other inflammatory diseases.

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典型和LINE1和the1a外显子il - 23r转录本在肉瘤性肌病中的异位共表达。

结节病是一种具有复杂遗传易感性的异质炎性疾病。多民族全基因组关联研究证实了结节病易感性与白细胞介素23受体基因（IL23R）单核苷酸变异的关联，该基因在肾上腺和睾丸中高度表达，但在骨骼肌中不表达。在这里，我们报道了与非SM疾病对照相比，在肉瘤性肌病（SM）中，一个典型的IL23R转录物同时异位表达和IL23R内含子6的选择性多腺苷化，导致在3'非翻译区（IL23RL1-THE1A）中含有两个反转录转座子LINE1 （L1PA16）和THE1A的新的异常转录物。RT-qPCR在另外一个样本集中证实了这两种转录本的表达，包括14个SM和29个非SM。我们还通过单核rna测序观察了这两种转录本在T细胞中的表达。这些发现应该为研究IL23R转录物变异在结节病易感性和其他炎症性疾病的遗传背景中的作用提供额外的资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Human Genetics 生物-遗传学

CiteScore

7.20

自引率

0.00%

发文量

101

审稿时长

4-8 weeks

期刊介绍： The Journal of Human Genetics is an international journal publishing articles on human genetics, including medical genetics and human genome analysis. It covers all aspects of human genetics, including molecular genetics, clinical genetics, behavioral genetics, immunogenetics, pharmacogenomics, population genetics, functional genomics, epigenetics, genetic counseling and gene therapy. Articles on the following areas are especially welcome: genetic factors of monogenic and complex disorders, genome-wide association studies, genetic epidemiology, cancer genetics, personal genomics, genotype-phenotype relationships and genome diversity.