Genome-wide analysis of the genetic regulation of gene expression in human neutrophils

人类中性粒细胞基因表达的遗传调控的全基因组分析

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作者:Anand Kumar Andiappan, Rossella Melchiotti, Tuang Yeow Poh, Michelle Nah, Kia Joo Puan, Elena Vigano, Doreen Haase, Nurhashikin Yusof, Boris San Luis, Josephine Lum, Dilip Kumar, Shihui Foo, Li Zhuang, Anusha Vasudev, Astrid Irwanto, Bernett Lee, Alessandra Nardin, Hong Liu, Furen Zhang, John Connol

Abstract

Neutrophils are an abundant immune cell type involved in both antimicrobial defence and autoimmunity. The regulation of their gene expression, however, is still largely unknown. Here we report an eQTL study on isolated neutrophils from 114 healthy individuals of Chinese ethnicity, identifying 21,210 eQTLs on 832 unique genes. Unsupervised clustering analysis of these eQTLs confirms their role in inflammatory responses and immunological diseases but also indicates strong involvement in dermatological pathologies. One of the strongest eQTL identified (rs2058660) is also the tagSNP of a linkage block reported to affect leprosy and Crohn's disease in opposite directions. In a functional study, we can link the C allele with low expression of the β-chain of IL18-receptor (IL18RAP). In neutrophils, this results in a reduced responsiveness to IL-18, detected both on the RNA and protein level. Thus, the polymorphic regulation of human neutrophils can impact beneficial as well as pathological inflammatory responses.

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