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.

Calcipotriol plus betamethasone dipropionate gel compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized, controlled trial investigating efficacy and safety in a Chinese population

“…Between 1 and 3% of Caucasians are affected, while the prevalence in East Asian populations is lower, between 0.2 and 1% . Recent genetic epidemiological studies have revealed a significant genetic basis, which may provide insights into mechanisms underlying such a disparity …”

“…[2][3][4][5] Recent genetic epidemiological studies have revealed a significant genetic basis, which may International Journal of Dermatology 2016, 55, 106-113 ª 2015 The International Society of Dermatology provide insights into mechanisms underlying such a disparity. [6][7][8] The scalp is one of the sites most commonly affected by psoriasis; between 53% and 79% of subjects with psoriasis have been reported to have scalp involvement, 9 and the frequency of involvement increases with the duration of the disease. 10 Scalp lesions are often welldemarcated, thickened, red, and scaly.…”

Whole exome sequencing identified two point mutations of COL7A1 and FLG in a Chinese family with dystrophic epidermolysis bullous pruriginosa and ichthyosis vulgaris

“…In addition, all these conditions present with pruritus. The FLG (c.7249C>T, p.Q2417X) mutation has also been identified in Chinese psoriasis vulgaris and atopic dermatitis patients . However, Schumann et al .…”

Ichthyosis Vulgaris and Other Disorders of Cornification

“…One study has suggested a relationship between a p.K4022X FLG mutation and psoriasis vulgaris in a patient with a family history of concomitant psoriasis and IV [ 85 ].…”