Genetic Interactions of Phase II Xenobiotic-Metabolizing Enzymes GSTO1 and GCLC in Relation to Alcohol Abuse and Psoriasis Risk

TL;DR

This study explores how genetic variations in GSTO1 and GCLC genes, along with alcohol abuse, may increase the risk of psoriasis, particularly in women.

Contribution

The first study to show that GSTO1 and GCLC gene polymorphisms and alcohol abuse jointly influence psoriasis risk.

Findings

The rs187304410-A allele and G/A genotype in GSTO1 are linked to lower psoriasis risk in females.

Epistatic interactions between GSTO1 and GCLC gene variants were identified as significant contributors to psoriasis risk.

Alcohol abuse was found to interact with genetic variants to influence psoriasis pathogenesis.

Abstract

The present pilot study aimed to investigate whether common single nucleotide polymorphisms (SNPs) in the gene encoding glutathione S-transferase omega 1 (GSTO1), both individually and in combination with variants of the catalytic subunit of the glutamate cysteine ligase (GCLC) gene and environmental risk factors, are associated with the risk of psoriasis. The research included a total of 944 participants, comprising 474 individuals diagnosed with psoriasis and 470 healthy control subjects. Five common SNPs in the GSTO1 gene—specifically, rs11191736, rs34040810, rs2289964, rs11191979, and rs187304410—were genotyped in the study groups using the MassARRAY-4 system. The allele rs187304410-A (OR = 0.19, 95% CI 0.04–0.86, Pperm = 0.02) and the genotype rs187304410-G/A (OR = 0.19, 95% CI 0.04–0.85, Pperm = 0.01) were found to be associated with psoriasis in females. The model-based multifactor dimensionality reduction approach facilitated the identification of higher-order epistatic interactions between the variants of the GSTO1 and GCLC genes (Pperm < 0.0001). These interactions, along with the risk factor of alcohol abuse, collectively contribute to the pathogenesis of psoriasis. This study is the first to demonstrate that polymorphisms in the GSTO1 gene, both individually and in combination with variants of the GCLC gene and alcohol abuse, are associated with an increased risk of psoriasis.

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