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

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 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 (Pperm ≤ 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.

Plaque Psoriasis Exacerbation and COVID-19 Vaccination: Assessing the Characteristics of the Flare and the Exposome Parameters

“…External exposome factors can also induce a psoriasis flare indirectly by modifying inner exposome factors (for example, oxidative stress triggered by tobacco [ 27 ]) as well as direct contributions to the pathogenesis pathways of psoriasis (nicotine stimulates the increased secretion of various cytokines) [ 28 ]. External exposome factors include environmental pollution, alcohol and tobacco abuse, as well as stress and sleep deprivation, diet, and lifestyle habits.…”

An Editorial on the Special Issue “Genetic Basis of Human Diseases”

“…Efanova et al’s work [ 13 ] proved, for the first time, the connection of GCLC gene’s polymorphism (which is involved in glutathione metabolism) with the development of a widespread skin disease, such as psoriasis. The authors demonstrated significant sex-specific features of the association of the GCLC gene’s genetic variant with the disease, the modifying effect of smoking/alcohol consumption on these associations and established significant correlations of the considered genetic determinants with various clinical signs, such as the disorder’s age of onset, the psoriatic triad and the nature of the target organ’s lesion—the skin.…”