Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Polymorphisms of the GCLC Gene Are Novel Genetic Markers For Susceptibility To Psoriasis Associated With Alcohol Abuse And Cigarette Smoking

Ekaterina Efanova
,
Olga Bushueva
ORCID logo ,
Roman Saranyuk
,
Anna Surovtseva
ORCID logo ,
Mikhail Churnosov
ORCID logo ,
Maria Solodilova
,
Alexey Polonikov
* ORCID logo
Version 1 : Received: 6 May 2023 / Approved: 8 May 2023 / Online: 8 May 2023 (08:03:11 CEST)

A peer-reviewed article of this Preprint also exists.

Efanova, E.; Bushueva, O.; Saranyuk, R.; Surovtseva, A.; Churnosov, M.; Solodilova, M.; Polonikov, A. Polymorphisms of the GCLC Gene Are Novel Genetic Markers for Susceptibility to Psoriasis Associated with Alcohol Abuse and Cigarette Smoking. Life 2023, 13, 1316. Efanova, E.; Bushueva, O.; Saranyuk, R.; Surovtseva, A.; Churnosov, M.; Solodilova, M.; Polonikov, A. Polymorphisms of the GCLC Gene Are Novel Genetic Markers for Susceptibility to Psoriasis Associated with Alcohol Abuse and Cigarette Smoking. Life 2023, 13, 1316.

Abstract

The aim of this pilot study was to investigate whether single nucleotide polymorphisms (SNP) in the gene encoding the catalytic subunit of glutamate cysteine ligase (GCLC) are associated with the risk and clinical features of psoriasis. A total of 944 unrelated individuals, including 474 patients with a diagnosis of psoriasis and 470 healthy controls, were recruited for the study. Six common SNPs in the GCLC gene were genotyped using the MassArray-4 system. Polymorphisms rs648595 (OR=0.56 95%CI 0.35-0.90, Pperm=0.017) and rs2397147 (OR=0.54 95%CI 0.30-0.98, Pperm=0.05) were associated with susceptibility to psoriasis in males. In the male group, diplotype rs2397147-C/C×rs17883901-G/G was associated with decreased risk of psoriasis (FDR-adjusted P=0.014), whereas diplotype rs6933870-G/G×rs17883901-G/G (FDR-adjusted P=0.045) showed association with increased disease risk in females. Joint effects of SNPs with tobacco smoking (rs648595 and rs17883901) and alcohol abuse (rs648595 and rs542914) on the risk of psoriasis were observed (Pperm≤0.05). Furthermore, we found multiple sex-independent associations between GCLC gene polymorphisms and various clinical features such as earlier disease onset, the psoriatic triad, and specific localizations of skin lesions. The present study is the first to show that polymorphisms of the GCLC gene are significantly associated with the risk of psoriasis and related to its clinical features.

Keywords

Psoriasis; genetic susceptibility; oxidative stress; glutathione; glutamate cysteine ligase; GCLC; single nucleotide polymorphism; cigarette smoking; alcohol abuse; gene–environment interactions

Subject

Medicine and Pharmacology, Dermatology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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