S Asad1, M C G Winge2, C-F Wahlgren3, K D Bilcha4, M Nordenskjöld5, F Taylan5, M Bradley5,3. 1. Department of Molecular Medicine & Surgery and the Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. samina.asad@ki.se. 2. Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA. 3. Dermatology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. 4. Department of Dermatovenereology, Faculty of Medicine, Gondar University, Gondar, Ethiopia. 5. Department of Molecular Medicine & Surgery and the Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
Abstract
BACKGROUND: The strong association between epidermal barrier gene variants and Atopic Dermatitis (AD) highlights that impaired skin barrier is a key feature in the pathogenesis of AD. Although the filaggrin (FLG) gene is the major AD risk gene in European and Asian populations, disease-associated variants remain elusive in African populations. OBJECTIVE: A previous study has reported that variants in the tight junction gene CLDN1 have been associated with AD susceptibility and disease severity in African-Americans. Our aim was therefore to investigate the association of CLDN1 with AD in the Ethiopian population. METHODS: To investigate how CLDN1 variants may be involved in increasing the risk of AD in the Ethiopian population, we analysed whole exome sequencing (WES) data for all exons in CLDN1, and in addition, assayed four SNPs (rs17501010, rs9290927, rs9290929 and rs893051) which had previously showed association in African-American AD patients. RESULTS: No damaging variants were detected through WES in 22 Ethiopian samples. Genotyping of disease-associated CLDN1 SNPs in Ethiopian cases and control material showed no overall association. However, significant association was seen for rs893051 in patients who developed AD before the age of 5 years (P < 0.03). CONCLUSION: Taken together, we demonstrate that tight junction genes and, in particular, CLDN1 rather than variants in FLG may be involved in the susceptibility of AD in the Ethiopian population.
BACKGROUND: The strong association between epidermal barrier gene variants and Atopic Dermatitis (AD) highlights that impaired skin barrier is a key feature in the pathogenesis of AD. Although the filaggrin (FLG) gene is the major AD risk gene in European and Asian populations, disease-associated variants remain elusive in African populations. OBJECTIVE: A previous study has reported that variants in the tight junction gene CLDN1 have been associated with AD susceptibility and disease severity in African-Americans. Our aim was therefore to investigate the association of CLDN1 with AD in the Ethiopian population. METHODS: To investigate how CLDN1 variants may be involved in increasing the risk of AD in the Ethiopian population, we analysed whole exome sequencing (WES) data for all exons in CLDN1, and in addition, assayed four SNPs (rs17501010, rs9290927, rs9290929 and rs893051) which had previously showed association in African-American ADpatients. RESULTS: No damaging variants were detected through WES in 22 Ethiopian samples. Genotyping of disease-associated CLDN1 SNPs in Ethiopian cases and control material showed no overall association. However, significant association was seen for rs893051 in patients who developed AD before the age of 5 years (P < 0.03). CONCLUSION: Taken together, we demonstrate that tight junction genes and, in particular, CLDN1 rather than variants in FLG may be involved in the susceptibility of AD in the Ethiopian population.
Authors: Sophia Bergmann; Barbara von Buenau; Sabine Vidal-Y-Sy; Marek Haftek; Ewa Wladykowski; Pia Houdek; Susanne Lezius; Hélène Duplan; Katja Bäsler; Stephan Dähnhardt-Pfeiffer; Christian Gorzelanny; Stefan W Schneider; Elke Rodriguez; Dora Stölzl; Stephan Weidinger; Johanna M Brandner Journal: Sci Rep Date: 2020-02-06 Impact factor: 4.379