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

被引：22

作者：

Andiappan, Anand Kumar ^{[1
]}

Melchiotti, Rossella ^{[1
]}

Poh, Tuang Yeow ^{[1
]}

Nah, Michelle ^{[1
]}

Puan, Kia Joo ^{[1
]}

Vigano, Elena ^{[1
]}

Haase, Doreen ^{[1
]}

Yusof, Nurhashikin ^{[1
]}

Luis, Boris San ^{[1
]}

Lum, Josephine ^{[1
]}

Kumar, Dilip ^{[1
]}

Foo, Shihui ^{[1
]}

Zhuang, Li ^{[1
]}

Vasudev, Anusha ^{[1
]}

Irwanto, Astrid ^{[2
]}

Lee, Bernett ^{[1
]}

Nardin, Alessandra ^{[1
]}

Liu, Hong ^{[3
,4
,5
,6
]}

Zhang, Furen ^{[3
,4
,5
,6
]}

Connolly, John ^{[1
]}

Liu, Jianjun ^{[2
,7
]}

Mortellaro, Alessandra ^{[1
]}

Wang, De Yun ^{[8
]}

Poidinger, Michael ^{[1
]}

Larbi, Anis ^{[1
]}

Zolezzi, Francesca ^{[1
]}

Rotzschke, Olaf ^{[1
]}

机构：

[1] ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore

[2] GIS, Dept Human Genet, Singapore, Singapore

[3] Shandong Univ, Shandong Prov Hosp Skin Dis, Jinan 250100, Shandong, Peoples R China

[4] Shandong Acad Med Sci, Shandong Prov Inst Dermatol & Venereol, Jinan, Shandong, Peoples R China

[5] Shandong Univ, Sch Med, Shandong Prov Med Ctr Dermatovenereol, Jinan 250100, Shandong, Peoples R China

[6] Prov Acad Med Sci, Shandong Prov Inst Dermatol & Venereol, Jinan, Shandong, Peoples R China

[7] Anhui Med Univ, Sch Life Sci, Hefei, Anhui, Peoples R China

[8] Natl Univ Singapore, Dept Otolaryngol, Singapore 117548, Singapore

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

INNATE IMMUNE-RESPONSE; EXTRACELLULAR TRAPS; ATOPIC-DERMATITIS; PSORIASIS; CELLS; TRANSCRIPTOME; INFLAMMATION; INDUCTION; ROLES;

D O I：

10.1038/ncomms8971

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta-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.

引用

页数：9

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