BACKGROUND: Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD. OBJECTIVES: To investigate further the spectrum of FLG-null mutations in Chinese patients and to compare it with that in other populations. METHODS: We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate-to-severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls. Results In total, 22 FLG-null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD [Fisher's exact test; P = 5·3 × 10⁻⁹; odds ratio (OR) 3·3], palmar hyperlinearity (Fisher's exact test; P = 9·0 × 10⁻¹⁵; OR 5·8), keratosis pilaris (Fisher's exact test; P = 0·001; OR 4·7) and with increased severity of AD (permutation test; P = 0·0063). CONCLUSIONS: This study emphasizes the wider genetic landscape of FLG-null mutations in Asia that is slowly emerging.
BACKGROUND: Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD. OBJECTIVES: To investigate further the spectrum of FLG-null mutations in Chinese patients and to compare it with that in other populations. METHODS: We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate-to-severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls. Results In total, 22 FLG-null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD [Fisher's exact test; P = 5·3 × 10⁻⁹; odds ratio (OR) 3·3], palmar hyperlinearity (Fisher's exact test; P = 9·0 × 10⁻¹⁵; OR 5·8), keratosis pilaris (Fisher's exact test; P = 0·001; OR 4·7) and with increased severity of AD (permutation test; P = 0·0063). CONCLUSIONS: This study emphasizes the wider genetic landscape of FLG-null mutations in Asia that is slowly emerging.
Authors: Kern Rei Chng; Angeline Su Ling Tay; Chenhao Li; Amanda Hui Qi Ng; Jingjing Wang; Bani Kaur Suri; Sri Anusha Matta; Naomi McGovern; Baptiste Janela; Xuan Fei Colin C Wong; Yang Yie Sio; Bijin Veonice Au; Andreas Wilm; Paola Florez De Sessions; Thiam Chye Lim; Mark Boon Yang Tang; Florent Ginhoux; John E Connolly; E Birgitte Lane; Fook Tim Chew; John E A Common; Niranjan Nagarajan Journal: Nat Microbiol Date: 2016-07-11 Impact factor: 17.745
Authors: Michelle Janssens; Jeroen van Smeden; Gert S Gooris; Wim Bras; Guiseppe Portale; Peter J Caspers; Rob J Vreeken; Thomas Hankemeier; Sanja Kezic; Ron Wolterbeek; Adriana P Lavrijsen; Joke A Bouwstra Journal: J Lipid Res Date: 2012-09-28 Impact factor: 5.922
Authors: David J Margolis; Andrea J Apter; Jayanta Gupta; Ole Hoffstad; Maryte Papadopoulos; Linda E Campbell; Aileen Sandilands; W H Irwin McLean; Tim R Rebbeck; Nandita Mitra Journal: J Allergy Clin Immunol Date: 2012-08-27 Impact factor: 10.793
Authors: Anne M Brauweiler; Lianghua Bin; Byung Eui Kim; Michiko K Oyoshi; Raif S Geha; Elena Goleva; Donald Y M Leung Journal: J Allergy Clin Immunol Date: 2012-12-11 Impact factor: 10.793