1] Division of Genetics and Molecular Medicine, King's College London, London SE1 9RT, UK [2].
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.
Nat Commun. 2014 Jun 13;5:4020. doi: 10.1038/ncomms5020.
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, Pcombined=3.23 × 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P(combined) = 4.58 × 10(-9), OR = 1.17) and 1q41 (rs1159268, P(combined) = 4.08 × 10(-8), OR = 1.17). All three loci contain genes linked to the TGFβ 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 TGFβ-mediated signalling in susceptibility to acne.
寻常痤疮（痤疮）是一种常见的皮肤毛发皮脂腺单位的炎症性疾病。在这里，我们在英国进行了全基因组关联分析，将严重痤疮病例（n=1893）与对照组（n=5132）进行比较。在第二阶段，我们在另外 2063 例痤疮病例和 1970 例对照中对假定相关的基因座进行基因分型。我们确定了三个全基因组显著关联：11q13.1（rs478304，P 联合=3.23×10(-11)，优势比（OR）=1.20），5q11.2（rs38055，P 联合=4.58×10(-9)，OR=1.17）和 1q41（rs1159268，P 联合=4.08×10(-8)，OR=1.17）。这三个基因座都包含与 TGFβ 细胞信号通路相关的基因，即 OVOL1、FST 和 TGFB2。与正常皮肤相比，OVOL1 和 TFGB2 的转录物在受影响的皮肤中表达减少。总的来说，这些数据支持 TGFβ 介导的信号通路失调在痤疮易感性中的关键作用。
