Investigation of Gamma Secretase Gene Complex Mutations in German Population with Hidradenitis Suppurativa Designates a Complex Polygenic Heritage

2021 ◽  
Author(s):  
Seçil Vural ◽  
Mark Baumgartner ◽  
Peter Lichtner ◽  
Gertrud Eckstein ◽  
Housien Hariry ◽  
...  
Keyword(s):  
Hidradenitis Suppurativa ◽  
German Population ◽  
Gene Complex ◽  
Gamma Secretase

Hidradenitis Suppurativa: Proposal of Classification in Two Endotypes with Two-Step Cluster Analysis

Dermatology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Anxo González-Manso ◽  
Eugènia Agut-Busquet ◽  
Jorge Romaní ◽  
Eva Vilarrasa ◽  
Flavia Bittencourt ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Tobacco Use ◽  
Pilonidal Sinus ◽  
Early Onset ◽  
Hidradenitis Suppurativa ◽  
Clinical Manifestations ◽  
Clinical Impression ◽  
Gamma Secretase ◽  
Serum Concentrations ◽  
History Of

<b><i>Introduction:</i></b> Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent disorder of the pilosebaceous unit. Currently, several attempts have been made to classify this disease according to its pathogenesis and clinical manifestations. We attempted at classifying 103 patients using two-step cluster analysis. <b><i>Methods:</i></b> The final model included body mass index, C-reactive protein (CRP), and serum concentrations of IL-1, IL-6, IL-17, and IL-10 as continuous variables, and sex, later/early onset, anterior/posterior lesion sites, presence/absence of sinus tracts, nodules and abscesses, positive/negative history of pilonidal sinus, and presence/absence of mutations in gamma-secretase subunits (APH1A, APH1B, MEFV, NCSTN, PSEN1, PSEN2, PSENEN, PSTPIP1) as qualitative variables. <b><i>Results:</i></b> The resultant model defined two groupings or clusters: cluster 1 (64.9% of patients) characterized by nonobese males, with nodular lesions in posterior sites, early-onset HS, higher IL-10, presence of gamma-secretase mutations, and history of pilonidal sinus; and cluster 2 (35.1% of patients) characterized by obese females or males, with lesions in anterior sites, more presence of sinus tracts and abscesses and less nodules, later-onset HS, and higher concentrations of IL-1, CRP, IL-17, and IL-6. Severity measures (Hurley, HS-PGA, and IHS4) and tobacco use were discarded because the analysis found them to be less relevant for clustering. <b><i>Conclusion:</i></b> Our resultant model confirms the clinical impression that HS is a disease spectrum with two pathogenic poles defining two clusters or endotypes. The probability of having severe disease was equally distributed in the two clusters. The variable with the highest predictive value for clustering was involvement of typical anterior sites (axillae, submammary) or atypical posterior sites (back, gluteal). Serum concentrations of interleukins, tobacco use, and sex had a lower predictive power for clustering.

scholarly journals Hidradenitis suppurativa: haploinsufficiency of gamma-secretase components does not affect gamma-secretase enzyme activityin vitro

2016 ◽  
Vol 175 (3) ◽  
pp. 632-635 ◽  
Author(s):  
A.E. Pink ◽  
D. Dafou ◽  
N. Desai ◽  
O. Holmes ◽  
C. Hobbs ◽  
...  
Keyword(s):  
Hidradenitis Suppurativa ◽  
Gamma Secretase

scholarly journals Hidradenitis Suppurativa-Like Lesions Associated with Pharmacologic Inhibition of Gamma-Secretase

2018 ◽  
Vol 138 (4) ◽  
pp. 979-981 ◽  
Author(s):  
Geraldine O’Sullivan Coyne ◽  
Therese S. Woodring ◽  
Chyi-Chia R. Lee ◽  
Alice P. Chen ◽  
Heidi H. Kong
Keyword(s):  
Hidradenitis Suppurativa ◽  
Gamma Secretase ◽  
Pharmacologic Inhibition

Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

2002 ◽  
Vol 38 ◽  
pp. 37-49 ◽  
Author(s):  
Janelle Nunan ◽  
David H Small
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Alternative Pathway ◽  
Protein A ◽  
Proteolytic Processing ◽  
Gamma Secretase ◽  
Amyloid Beta Protein ◽  
Protein Precursor ◽  
Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

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