Polymorphisms of the GCLC Gene Are Novel Genetic Markers for Susceptibility to Psoriasis Associated with Alcohol Abuse and Cigarette Smoking

Ekaterina Efanova; Olga Bushueva; Roman Saranyuk; Anna Surovtseva; Mikhail Churnosov; Maria Solodilova; Alexey Polonikov

doi:10.3390/life13061316

Polymorphisms of the GCLC Gene Are Novel Genetic Markers for Susceptibility to Psoriasis Associated with Alcohol Abuse and Cigarette Smoking

Life (Basel). 2023 Jun 2;13(6):1316. doi: 10.3390/life13061316.

Authors

Ekaterina Efanova^{1

2}, Olga Bushueva^{2

3}, Roman Saranyuk^{2

4}, Anna Surovtseva², Mikhail Churnosov⁵, Maria Solodilova³, Alexey Polonikov^{3

6}

Affiliations

¹ Medvenka Central District Hospital, 68 Sovetskaya Street, 307030 Kursk, Russia.
² Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya Street, 305041 Kursk, Russia.
³ Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, 305041 Kursk, Russia.
⁴ Center for Medical Examinations and Prevention, 2 Leninsky Komsomol Avenue, 305026 Kursk, Russia.
⁵ Department of Medical Biological Disciplines, Belgorod State University, 85 Pobedy Street, 308015 Belgorod, Russia.
⁶ Laboratory of Statistical Genetics and Bioinformatics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 18 Yamskaya Street, 305041 Kursk, Russia.

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; P_perm = 0.017) and rs2397147 (OR = 0.54, 95% CI 0.30-0.98; P_perm = 0.05) were associated with susceptibility to psoriasis in males. In the male group, diplotype rs2397147-C/C × rs17883901-G/G was associated with a decreased risk of psoriasis (FDR-adjusted p = 0.014), whereas diplotype rs6933870-G/G × rs17883901-G/G (FDR-adjusted p = 0.045) showed an association with an increased disease risk in females. The joint effects of SNPs with tobacco smoking (rs648595 and rs17883901) and alcohol abuse (rs648595 and rs542914) on psoriasis risk were observed (P_perm ≤ 0.05). We also 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: GCLC; alcohol abuse; cigarette smoking; genetic susceptibility; gene–environment interactions; glutamate cysteine ligase; glutathione; oxidative stress; psoriasis; single nucleotide polymorphism.

Grants and funding

This research received no external funding.