γ分泌酶基因突变在反常性痤疮的研究进展

doi:10.3760/cma.j.issn.0412-4030.2019.09.015

中华皮肤科杂志 ›› 2019, Vol. 52 ›› Issue (9): 656-659.doi: 10.3760/cma.j.issn.0412-4030.2019.09.015

γ分泌酶基因突变在反常性痤疮的研究进展

周鹏军¹ 王宝玺² 林立航³ 肖学敏³

¹福建医科大学研究生院，福州 350001；²中国医学科学院北京协和医学院整形外科医院皮肤科，北京 100144；³福建医科大学附属协和医院皮肤科，福州 350001

收稿日期:2018-06-26 修回日期:2019-01-25 出版日期:2019-09-15 发布日期:2019-08-30
通讯作者: 肖学敏；林立航 E-mail:258260101@qq.com; 460879404@qq.com
基金资助:
国家自然科学基金（81602785）

γ-Secretase mutations in acne inversa

Zhou Pengjun¹, Wang Baoxi², Lin Lihang³, Xiao Xuemin³#br# #br#

¹Graduate School of Fujian Medical University, Fuzhou 350001, China; ²Department of Dermatology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, China; ³Department of Dermatology, Fujian Medical University Union Hospital, Fuzhou 350001, China

Received:2018-06-26 Revised:2019-01-25 Online:2019-09-15 Published:2019-08-30
Contact: Xiao Xuemin; Lin Lihang E-mail:258260101@qq.com; 460879404@qq.com
Supported by:
National Natural Science Foundation of China （81602785）

摘要/Abstract

摘要： 【摘要】反常性痤疮是毛囊-皮脂腺-顶泌汗腺单元的慢性炎症性皮肤病，遗传和免疫因素是目前发病机制研究的热点。遗传因素主要与γ分泌酶突变有关：在γ分泌酶基因单倍体不足的遗传背景下，部分患者γ分泌酶-Notch轴表达异常，导致毛囊角化和炎症加剧。γ分泌酶基因突变并不一定引起反常性痤疮的发生，家族性反常性痤疮患者阿尔茨海默病的发病风险仍不清楚，基因型和表型的联系已取得一定的进展，但还需大样本研究的验证。

关键词: 化脓性汗腺炎； γ-分泌酶；突变；受体, Notch；发病机制

Abstract: 【Abstract】 Acne inversa is a chronic inflammatory skin disease of the folliculo-sebaceous-apocrine unit. Currently， genetic and immunological factors are hot topics in the study of its pathogenesis. Genetic factors are mainly related to γ-secretase mutations, and abnormal expression of the γ-secretase-Notch axis leads to increased keratinization of hair follicles and inflammation in some patients with haploinsufficiency of the γ-secretase gene. Mutations in the γ-secretase gene are not necessary for acne inversa, and the risk of Alzheimer′s disease in familial acne inversa patients still remains unclear. Some progress has been made in researches on the association of genotype with phenotype in acne inversa patients, but further studies with large sample size are needed for verification.

Key words: Hidradenitis suppurativa , γ-Secretase, Mutation, Receptors, Notch, Pathogenesis

周鹏军王宝玺林立航肖学敏. γ分泌酶基因突变在反常性痤疮的研究进展[J]. 中华皮肤科杂志, 2019, 52(9): 656-659.doi:10.3760/cma.j.issn.0412-4030.2019.09.015

Zhou Pengjun, Wang Baoxi, Lin Lihang, Xiao Xuemin. γ-Secretase mutations in acne inversa[J]. Chinese Journal of Dermatology, 2019, 52(9): 656-659.doi:10.3760/cma.j.issn.0412-4030.2019.09.015

参考文献 24

［1］	Ingram JR. The genetics of hidradenitis suppurativa［J］. Dermatol Clin, 2016,34（1）:23⁃28. doi: 10.1016/j.det.2015.07.002.
［2］	Wang B, Yang W, Wen W, et al. Gamma⁃secretase gene mutations in familial acne inversa［J］. Science, 2010,330（6007）:1065. doi: 10.1126/science.1196284.
［3］	Li C, Li W, Xu H, et al. PSENEN mutation carriers with co⁃manifestation of acne inversa （AI） and Dowling⁃Degos disease （DDD）: is AI or DDD the subphenotype?［J］. J Invest Dermatol, 2017,137（10）:2234⁃2236. doi: 10.1016/j.jid.2017.05.021.
［4］	Pink A, Anzengruber F, Navarini AA. Acne and hidradenitis suppurativa［J］. Br J Dermatol, 2018,178（3）:619⁃631. doi: 10. 1111/bjd.16231.
［5］	Carroll CM, Li YM. Physiological and pathological roles of the γ⁃secretase complex［J］. Brain Res Bull, 2016,126（Pt 2）:199⁃206. doi: 10.1016/j.brainresbull.2016.04.019.
［6］	ARJV V, van der Zee HH, Prens EP. Sequence variants in hidradenitis suppurativa: in search of the pathogenic mechanisms［J］. Br J Dermatol, 2017,177（4）:895⁃896. doi: 10. 1111/bjd.15812.
［7］	Xiao X, He Y, Li C, et al. Nicastrin mutations in familial acne inversa impact keratinocyte proliferation and differentiation through the Notch and phosphoinositide 3⁃kinase AKT signalling pathways［J］. Br J Dermatol, 2016,174（3）:522⁃532. doi: 10.1111/ bjd.14223.
［8］	Pink AE, Dafou D, Desai N, et al. Hidradenitis suppurativa: haploinsufficiency of gamma⁃secretase components does not affect gamma⁃secretase enzyme activity in vitro［J］. Br J Dermatol, 2016,175（3）:632⁃635. doi: 10.1111/bjd.14621.
［9］	Zhang X, Sisodia SS. Acne inversa caused by missense mutations in NCSTN is not fully compatible with impairments in Notch signaling［J］. J Invest Dermatol, 2015,135（2）:618⁃620. doi: 10. 1038/jid.2014.399.
［10］	JAM M, Ojala VK, Knittle AM, et al. Genome⁃wide screen of gamma⁃secretase⁃mediated intramembrane cleavage of receptor tyrosine kinases［J］. Mol Biol Cell, 2017,28（22）:3123⁃3131. doi: 10.1091/mbc.e17⁃04⁃0261.
［11］	Savva A, Kanni T, Damoraki G, et al. Impact of Toll⁃like receptor⁃4 and tumour necrosis factor gene polymorphisms in patients with hidradenitis suppurativa［J］. Br J Dermatol, 2013,168（2）:311⁃317. doi: 10.1111/bjd.12105.
［12］	Ingram JR, Wood M, John B, et al. Absence of pathogenic γ⁃secretase mutations in a South Wales cohort of familial and sporadic hidradenitis suppurativa （acne inversa）［J］. Br J Dermatol, 2013,168（4）:874⁃876. doi: 10.1111/bjd.2013.168.issue⁃4.
［13］	Fitzsimmons JS, Guilbert PR, Fitzsimmons EM. Evidence of genetic factors in hidradenitis suppurativa［J］. Br J Dermatol, 1985,113（1）:1⁃8.
［14］	肖学敏, 李诚让, 何艳艳, 等. Nicastrin基因突变的反常性痤疮患者皮损Notch⁃HES信号通路的表达［J］. 中华皮肤科杂志, 2016,49（6）:415⁃419. doi: 10.3760/cma.j.issn.0412⁃4030. 2016.06.012.
［15］	Melnik BC, Plewig G. Impaired Notch⁃MKP⁃1 signalling in hidradenitis suppurativa: an approach to pathogenesis by evidence from translational biology［J］. Exp Dermatol, 2013,22（3）:172⁃177. doi: 10.1111/exd.12098.
［16］	Melnik BC, John SM, Chen W, et al. T helper 17 cellregulatory T⁃cell imbalance in hidradenitis suppurativaacne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities［J］. Br J Dermatol, 2018,179（2）:260⁃272. doi: 10.1111/bjd.2018.179.issue⁃6.
［17］	Jurisch⁃Yaksi N, Sannerud R, Annaert W. A fast growing spectrum of biological functions of gamma⁃secretase in development and disease［J］. Biochim Biophys Acta, 2013,1828（12）:2815⁃2827. doi: 10.1016/j.bbamem.2013.04.016.
［18］	Duchatelet S, Miskinyte S, Join⁃Lambert O, et al. First nicastrin mutation in PASH （pyoderma gangrenosum, acne and suppurative hidradenitis） syndrome［J］. Br J Dermatol, 2015,173（2）:610⁃612. doi: 10.1111/bjd.13668.
［19］	Garg A, Strunk A. Risk of Alzheimer′s disease is not increased among patients with hidradenitis suppurativa: a retrospective population⁃based cohort analysis［J］. J Am Acad Dermatol, 2017,77（1）:176⁃177. doi: 10.1016/j.jaad.2017.02.055.
［20］	Panmontha W, Rerknimitr P, Yeetong P, et al. A frameshift mutation in PEN⁃2 causes familial comedones syndrome［J］. Dermatology, 2015,231（1）:77⁃81. doi: 10.1159/000382122.
［21］	Deckers IE, van der Zee HH, Boer J, et al. Correlation of early⁃onset hidradenitis suppurativa with stronger genetic suscepti⁃bility and more widespread involvement［J］. J Am Acad Dermatol, 2015,72（3）:485⁃488. doi: 10.1016/j.jaad.2014.11.017.
［22］	Canoui⁃Poitrine F, Le Thuaut A, Revuz JE, et al. Identification of three hidradenitis suppurativa phenotypes: latent class analysis of a cross⁃sectional study［J］. J Invest Dermatol, 2013,133（6）:1506⁃1511. doi: 10.1038/jid.2012.472.
［23］	Ingram JR, Piguet V. Phenotypic heterogeneity in hidradenitis suppurativa （acne inversa）: classification is an essential step toward personalized therapy［J］. J Invest Dermatol, 2013,133（6）:1453⁃1456. doi: 10.1038/jid.2012.476.
［24］	Xu H, Xiao X, Hui Y, et al. Phenotype of 53 Chinese individuals with nicastrin gene mutations in association with familial hidradenitis suppurativa （acne inversa）［J］. Br J Dermatol, 2016,174（4）:927⁃929. doi: 10.1111/bjd.2016.174.issue⁃4.

γ分泌酶基因突变在反常性痤疮的研究进展

γ-Secretase mutations in acne inversa

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