Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy

Yonghu Sun, Astrid Irwanto, Licht Toyo-Oka, Myunghee Hong, Hong Liu, Anand Kumar Andiappan, Hyunchul Choi, Yuki Hitomi, Gongqi Yu, Yongxiang Yu, Fangfang Bao, Chuan Wang, Xian Fu, Zhenhua Yue, Honglei Wang, Huimin Zhang, Minae Kawashima, Kaname Kojima, Masao Nagasaki, Minoru NakamuraSuk Kyun Yang, Byong Duk Ye, Yosua Denise, Olaf Rotzschke, Kyuyoung Song, Katsushi Tokunaga, Furen Zhang, Jianjun Liu

研究成果: Article査読

9 被引用数 (Scopus)

抄録

Genetic polymorphism within the 9q32 locus is linked with increased risk of several diseases, including Crohn's disease (CD), primary biliary cholangitis (PBC) and leprosy. The most likely disease-causing gene within 9q32 is TNFSF15, which encodes the pro-inflammatory cytokine TNF super-family member 15, but it was unknown whether these disparate diseases were associated with the same genetic variance in 9q32, and how variance within this locus might contribute to pathology. Using genetic data from published studies on CD, PBC and leprosy we revealed that bearing a T allele at rs6478108/rs6478109 (r 2 = 1) or rs4979462 was significantly associated with increased risk of CD and decreased risk of leprosy, while the T allele at rs4979462 was associated with significantly increased risk of PBC. In vitro analyses showed that the rs6478109 genotype significantly affected TNFSF15 expression in cells from whole blood of controls, while functional annotation using publicly-available data revealed the broad cell type/tissue-specific regulatory potential of variance at rs6478109 or rs4979462. In summary, we provide evidence that variance within TNFSF15 has the potential to affect cytokine expression across a range of tissues and thereby contribute to protection from infectious diseases such as leprosy, while increasing the risk of immune-mediated diseases including CD and PBC.

本文言語English
論文番号31429
ジャーナルScientific reports
6
DOI
出版ステータスPublished - 2016 8 10

ASJC Scopus subject areas

  • 一般

フィンガープリント

「Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease and leprosy」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル