A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population.

Background: A pathogenetic factor of ischemic stroke (IS) is oxidative stress. As a rate-limiting enzyme constituent in the glutathione synthetic pathway, the glutamate-cysteine ligase catalytic subunit (GCLC) exerts a crucial effect on the redox homeostasis. Several studies have shown that variants of the GCLC gene are related to susceptibility to various diseases. However, the association between GCLC single nucleotide polymorphisms (SNPs) and IS susceptibility has rarely been explored in the Chinese population. This study investigated the correlation of GCLC SNPs with the IS susceptibility in a southern Han Chinese population.

Methods: In this study, 400 controls and 388 IS patients were enrolled, and clinical data were collected. Six polymorphisms at GCLC were genotyped using an SNPscan kit.

Results: The results revealed that rs12524494 GG at GCLC was linked to a markedly lowered probability of IS development (GG vs. AA: adjusted OR = 0.42, 95% CI, 0.20-0.91, p = 0.027; GG vs. AG + AA: adjusted OR = 0.41, 95% CI, 0.19-0.86, P = 0.018). Lipid analysis results revealed lower high-density lipoprotein (HDL) levels (p = 0.017) along with higher triglyceride (TG) levels (p = 0.006) in IS patients with rs51008 GG. Moreover, higher homocysteine (Hcy) levels were detected in controls than in patients (p < 0.0001). Both controls and patients with rs12524494 GG had significantly lower Hcy levels than their counterparts who carried rs12524494 AA/AG (P < 0.05).

Conclusions: These results indicated that rs12524494 GG may be linked to decreasing IS susceptibility. The identified rs12524494 GG may serve as a potential biomarker for predicting IS susceptibility in the Chinese population, which could inform personalized medicine approaches for stroke prevention and treatment.