ORIGINAL RESEARCH

Filaggrin loss-of-function mutations 2282del4, R501X, R2447X and S3247X in atopic dermatitis

Verbenko DA, Karamova AE, Chickin VV, Kozlova IV, Aulova KM, Kubanov AA, Gorodnichev PV
About authors

State Research Center of Dermatovenereology and Cosmetology of the Ministry of Health of the Russian Federation

Correspondence should be addressed: Dmitry Anatolyevich Verbenko
Korolenko, 3/6, office 320, Moscow, 117076, Russia; moc.liamg@oknebrev

About paper

Funding: the research was financially supported by the Ministry of Health of the Russian Federation (State Task for the State Research Center of Dermatovenereology and Cosmetology № 056-00116-21-00-6 for 2021-2023).

Author contribution: AE Karamova, VV Chikin, KM Aulova, PV Gorodnichev — examination of patients, diagnosing, SCORAD calculation, obtaining informed consent, sampling patients' biomaterial; DA Verbenko — research planning, molecular genetic experiments, manuscript authoring; IV Kozlova — analysis of uniqueness of the oligonucleotides hybridizing to the loss-of-function mutations in the FLG gene; AE Karamova — manuscript editing; AA Kubanov — general guidance, manuscript editing.

Compliance with ethical standards: the study was approved by the Ethics Committee of the State Research Center of Dermatovenereology and Cosmetology (Minutes #1 of January 29, 2021), and meets the standards of good clinical practice and evidence-based medicine. All patients included in the study have read and signed a voluntary informed consent to participate therein.

Received: 2024-01-12 Accepted: 2024-02-10 Published online: 2024-02-25
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Atopic dermatitis (AD) is a widespread multifactorial genetically determined inflammatory skin disease caused by, among other causes, impaired functions of the epidermal barrier. Loss-of-function mutations of the filaggrin gene (important component of the natural moisturizing factor system) that arrest production of the full-fledged precursor protein are associated with AD. This work investigated the frequency of the 2282delACTG (rs558269137), R501X (rs61816761), S3247X (rs150597413), R2447X (rs138726443) loss-of-function mutations of the filaggrin gene in adult European patients with moderate to severe AD. The study involved 99 adult patients of both sexes aged 18-68 years. The mutations were identified with the help of the purpose-developed method of multiplex analysis of four single nucleotide polymorphisms that relies on the SNaPshot technique (minisequencing). The incidence of loss-of-function mutation of filaggrin 2282delACTG was 5.3%, that of R501X - 0.5%, R2447X - 1%. No S3247X mutation was detected in the sample. Collation of the results with Russian and European samples revealed a comparable level of the analyzed filaggrin gene mutations in adult patients with AD from different regions of the Russian Federation.

Keywords: SNP, atopic eczema, fillagrin, loss-of-function mutation, SNaPshot technique

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