Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

被引：62

作者：

Navarini, Alexander A. ^{[1
]}

Simpson, Michael A. ^{[1
]}

Weale, Michael ^{[1
]}

Knight, Jo ^{[2
]}

Carlavan, Isabelle ^{[3
]}

Reiniche, Pascale ^{[3
]}

Burden, David A. ^{[4
]}

Layton, Alison ^{[5
]}

Bataille, Veronique ^{[6
]}

Allen, Michael ^{[1
]}

Pleass, Robert ^{[7
]}

Pink, Andrew ^{[1
,7
]}

Creamer, Daniel ^{[8
]}

English, John ^{[9
]}

Munn, Stephanie ^{[10
]}

Walton, Shernaz ^{[11
]}

Willis, Carolyn ^{[12
]}

Deret, Sophie ^{[3
]}

Voegel, Johannes J. ^{[3
]}

Spector, Tim

Smith, Catherine H. ^{[7
]}

Trembath, Richard C. ^{[13
]}

Barker, Jonathan N. ^{[1
]}

机构：

[1] Kings Coll London, Div Genet & Mol Med, London SE1 9RT, England

[2] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON M5T 1R8, Canada

[3] Galderma R&D, Div Sci, F-06410 Sophia Antipolis, France

[4] Univ Glasgow, Western Infirm, Dept Dermatol, Glasgow G11 6NT, Lanark, Scotland

[5] Harrogate & Dist Fdn Trust, Dept Dermatol, Harrogate HG2 7SX, England

[6] Kings Coll London, Div Genet & Mol Med, Twin Res & Genet Epidemiol Unit, London SE1 7EH, England

[7] Guys & St Thomas NHS Fdn Trust, St Johns Inst Dermatol, London SE1 9RT, England

[8] Kings Coll Hosp NHS Fdn Trust, Dept Dermatol, London SE5 9RS, England

[9] Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Dept Dermatol, Nottingham NG7 2UJ, England

[10] Kings Coll Hosp NHS Fdn Trust, Orpington Hosp, Dept Dermatol, Orpington BR6 9JU, England

[11] NHS Trust & Hull York Med Sch, Hull & East Yorkshire Hosp, Kingston Upon Hull HU3 2JZ, N Humberside, England

[12] Buckinghamshire Healthcare NHS Trust, Amersham Hosp, Dept Dermatol, Amersham HP7 0JD, England

[13] Queen Mary Univ London, Barts & London Sch Med & Dent, London EC1M 6BQ, England

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

瑞士国家科学基金会; 英国医学研究理事会;

关键词：

TGF-BETA; SEBACEOUS GLANDS; GROWTH; DIFFERENTIATION; GENE; PROLIFERATION; MORPHOGENESIS; EXPRESSION; REGULATOR; DATABASE;

D O I：

10.1038/ncomms5020

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：

Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Here we perform a genome-wide association analysis in the United Kingdom, comparing severe cases of acne (n - 1,893) with controls (n - 5,132). In a second stage, we genotype putative-associated loci in a further 2,063 acne cases and 1,970 controls. We identify three genome-wide significant associations: 11q13.1 (rs478304, P-combined = 3.23 x 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P-combined = 4.58 x 10(-9), OR = 1.17) and 1q41 (rs1159268, P-combined = 4.08 x 10(-8), OR = 1.17). All three loci contain genes linked to the TGF beta cell signalling pathway, namely OVOL1, FST and TGFB2. Transcripts of OVOL1 and TFGB2 have decreased expression in affected compared with normal skin. Collectively, these data support a key role for dysregulation of TGF beta-mediated signalling in susceptibility to acne.

引用

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