Association of GPX4 rs713041 and rs4807542 polymorphisms and serum GPX4 levels in Chinese patients with systemic lupus erythematosus

Objectives: To investigate the association of serum glutathione peroxidase 4 (GPX4) levels and GPX4 polymorphisms with systemic lupus erythematosus (SLE) and lupus nephritis (LN) in a Chinese population. Methods: This hospital-based case–control study included 28 patients with LN, 28 patients with SLE without renal involvement, and 28 healthy controls for measurement of serum GPX4 levels using enzyme-linked immunosorbent assay (ELISA). In addition, 104 patients with SLE (including 64 with LN and 40 without renal involvement) and 100 healthy controls underwent genotyping of target single-nucleotide polymorphisms (SNPs) by polymerase chain reaction-coupled Sanger sequencing. Multivariable binary logistic regression analyses were performed to adjust for potential confounding factors. Results: Serum GPX4 levels were significantly lower in both the LN and non-LN groups than in the healthy control group, and GPX4 showed moderate diagnostic accuracy for SLE detection. In univariate analyses, carriers of the CC genotype and C allele at rs713041, as well as carriers of the GA genotype and A allele at rs4807542, had a significantly increased risk of SLE compared with healthy controls. Multivariable binary logistic regression further showed that the rs713041 CC genotype and rs4807542 A-carrier status remained independently associated with SLE susceptibility after adjustment for age and sex. Furthermore, in comparisons between LN and non-LN patients, carriers of the CC genotype and C allele at rs713041 were significantly associated with an increased risk of LN in univariate analyses, and the rs713041 CC genotype remained independently associated with renal involvement after adjustment for age, sex, disease duration, and SLEDAI score. Conclusions: Reduced serum GPX4 levels in both LN and non-LN patients suggest that GPX4 may be involved in the pathogenesis of SLE-related renal injury. In addition, GPX4 polymorphisms rs713041 and rs4807542 were independently associated with SLE susceptibility, whereas only rs713041 was independently associated with renal involvement in patients with SLE. These findings suggest that rs713041 may serve as a potential genetic marker of LN susceptibility in the Chinese population.