Τίτλος:
High Copy Numbers of β-Defensin Cluster on 8p23.1, Confer Genetic Susceptibility, and Modulate the Physical Course of Hidradenitis Suppurativa/Acne Inversa
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Hidradenitis suppurativa/acne inversa (HS) has a multifactorial pathogenesis, with many patients reporting positive family history. Nine β-defensin genes (among them DEFB4 and DEFB103, encoding for proinflammatory mediators human β-defensin–2 and human β-defensin–3, respectively) exist as a cluster (DEFB) affected by copy number (CN). We hypothesized that CNs are greater in patients with HS and that they are linked to genetic susceptibility. CNs of DEFB were studied in two independent patient cohorts: 163 patients from Greece and 98 from Germany. CNs were greater in patients than control subjects in both studied cohorts. Carriage of more than six CNs was associated with a 7.53 odds ratio for HS in the Greek cohort and a 5.76 odds ratio for HS in the German cohort. The common odds ratio after meta-analysis was 6.72 (P < 0.0001). However, presence of fewer than six copies was linked with disease onset at an earlier age (P = 0.048), less frequent presentation of permanent purulence of the affected skin lesions (P = 0.036), and fewer skin localizations (P = 0.042). A robust genetic trait for susceptibility to HS is provided, and this is confirmed in two independent cohorts. Susceptibility arises from carriage of more than six DEFB copies, which interferes directly with the HS phenotype. © 2016 The Authors
Συγγραφείς:
Giamarellos-Bourboulis, E.J.
Platzer, M.
Karagiannidis, I.
Kanni, T.
Nikolakis, G.
Ulrich, J.
Bellutti, M.
Gollnick, H.
Bauer, M.
Zouboulis, C.C.
Huse, K.
Περιοδικό:
Journal of Investigative Dermatology
Λέξεις-κλειδιά:
beta defensin; beta defensin; beta-defensin 3, human; DEFB4A protein, human, acne; adult; Article; case control study; comparative study; controlled study; copy number variation; female; genetic susceptibility; genetic trait; Germany; Greece; human; limit of detection; major clinical study; male; pathogenesis; phenotype; priority journal; prospective study; skin defect; suppurative hidradenitis; chromosome 8; clinical trial; cluster analysis; gene dosage; genetic predisposition; genetics; genotype; middle aged; multicenter study; multigene family; odds ratio; pathology; skin; suppurative hidradenitis, Adult; beta-Defensins; Case-Control Studies; Chromosomes, Human, Pair 8; Cluster Analysis; Female; Gene Dosage; Genetic Predisposition to Disease; Genotype; Germany; Greece; Hidradenitis Suppurativa; Humans; Male; Middle Aged; Multigene Family; Odds Ratio; Phenotype; Prospective Studies; Skin
DOI:
10.1016/j.jid.2016.04.021
