Clinical features of severe acne and genetic determinants of therapeutic efficacy of systemic isotretinoin

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OBJECTIVE

To study the clinical features of severe acne and pharmacogenetic mechanism of resistance to systemic therapy.

MATERIAL AND METHODS

A prospective open-label nonrandomized single-center comparative study was performed at the Department of Skin Diseases and Cosmetology of the Pirogov RNRMU in 2011—2024. The study included 388 subjects divided into 2 groups: study —309 patients with severe acne, comparison group — 79 conditionally healthy persons. Molecular genetic diagnosis was carried out by the method of next-generation sequencing (NGS) with the use of targeted multi-gene panels at the Laboratory of Molecular Biology of the Dmitry Rogachev NRCPHOI. Statistical processing of results was done by means of the Python language (Python 3.11.).

RESULTS

It has been established that the clinical features of severe acne are 2 clinical forms, namely severe papulopustulous acne, moderate nodular acne and severe nodular acne, acne conglobata in approximately equal proportion (49.5 and 50.5%, respectively). Thus, the pattern has been revealed: women suffered mainly from the first clinical form, men — from the second. We have demonstrated for the first time that the PTCH1 (rs574688) in intron, ABCA1 (rs2777801) in intron, RET (-(. ) in introns increase the risk of acne development by 2.85, 2.54 and 2.33 times, respectively (p<0.05); severe acne is associated with GA SMPD1 rs1050239 genotype. Strong inverse correlation between the GG SMPD1 rs1050239 genotype and the A SMPD1 rs1050239 allele and moderate inverse correlation between the GC PTCH1 rs574688 and GG SMPD1 rs1050239 genotypes have been found.

CONCLUSION

Detection of the specific loci of genes, regulation of the activation of response on retinoic acid and its derivatives can be pharmacogenetic markers of acne resistance.

Keywords:

acne

systemic isotretinoin

pharmacogenetic efficacy

Authors:

Demina O.M.

The Russian National Research Medical University named after N.I. Pirogov

ORCID: 0000-0001-9406-2787

Received:

02.12.2024

Accepted:

08.12.2024

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