title: Loss-of-function mutations in filaggrin gene associate with psoriasis vulgaris in Chinese population.
abstract: Loss-of-function mutations in filaggrin gene (FLG; OMIM #135940) have been reported to cause the semi-dominant keratinizing disorders such as ichthyosis vulgaris (IV; OMIM #146700) and atopic dermatitis (AD; OMIM #605803). Recent linkage analysis and immunohistochemical studies suggest the possible contribution of FLG to psoriatic susceptibility. However, no susceptibility variant in FLG gene associated with psoriasis (OMIM #177900) has been identified. In this study, we identified a non-sense mutation of FLG (p.K4022X) in a Chinese psoriasis/IV coexisting family. The homozygous p.K4022X mutation was detected in a psoriasis patient, whereas the heterozygous p.K4022X mutation was identified in two IV patients and four apparently normal family members. We also genotyped p.K4022X variant in 441 sporadic Chinese psoriasis patients and found homozygous mutation in two patients, while no homozygous variant was found in 500 control individuals. After sequencing the entire coding region of FLG gene in 441 psoriasis patients, we identified another five mutations (p.R826X, p.W2583X, c.7945delA, c.3321delA and p.Q2417X). Although all six FLG mutations as a whole was not significantly associated with psoriasis (P = 0.105), mutation p.K4022X was significantly associated with psoriasis (P < 0.05). Our data thus indicates an association of FLG with psoriasis in Chinese population.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xiong
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Xu
authors.forename: Fangfang
authors.initials: F
authors.lastname: Li
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.forename: Yalan
authors.initials: Y
authors.lastname: Liu
authors.forename: Deyuan
authors.initials: D
authors.lastname: Liu
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Xie
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.forename: Yehong
authors.initials: Y
authors.lastname: Kuang
authors.forename: Lisha
authors.initials: L
authors.lastname: Wu
authors.forename: Jianglin
authors.initials: J
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Pan
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D005260:Female; D000091344:Filaggrin Proteins; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011565:Psoriasis / Q000208:ethnology* / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins