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