A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population
Abstract 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...
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BMC
2025-05-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02688-z |
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| author | Tao Liao Yin-Hua Weng Jiang He Mei-Rong Chen Yu Chen Zhong-Quan Qi Zheng-Mian Zhang |
| author_facet | Tao Liao Yin-Hua Weng Jiang He Mei-Rong Chen Yu Chen Zhong-Quan Qi Zheng-Mian Zhang |
| author_sort | Tao Liao |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-2391b8bc3f054907a3cb1f656085705b |
| institution | DOAJ |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-2391b8bc3f054907a3cb1f656085705b2025-08-20T03:22:12ZengBMCEuropean Journal of Medical Research2047-783X2025-05-0130111110.1186/s40001-025-02688-zA genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese populationTao Liao0Yin-Hua Weng1Jiang He2Mei-Rong Chen3Yu Chen4Zhong-Quan Qi5Zheng-Mian Zhang6School of Medicine, Guangxi UniversitySchool of Clinical Medicine, Guilin Medical UniversityAcupuncture and Moxibustion and Tuina College, Guangxi University of Chinese MedicineSchool of Medicine, Guangxi UniversityDepartment of Rheumatology, Guilin Medical UniversitySchool of Medicine, Guangxi UniversityFujian Maternity and Child Health HospitalAbstract 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.https://doi.org/10.1186/s40001-025-02688-zIschemic strokeGCLCSingle nucleotide polymorphismHomocysteineSusceptibility |
| spellingShingle | Tao Liao Yin-Hua Weng Jiang He Mei-Rong Chen Yu Chen Zhong-Quan Qi Zheng-Mian Zhang A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population European Journal of Medical Research Ischemic stroke GCLC Single nucleotide polymorphism Homocysteine Susceptibility |
| title | A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population |
| title_full | A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population |
| title_fullStr | A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population |
| title_full_unstemmed | A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population |
| title_short | A genetic variant of the glutamate-cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the Chinese population |
| title_sort | genetic variant of the glutamate cysteine ligase catalytic subunit is associated with susceptibility to ischemic stroke in the chinese population |
| topic | Ischemic stroke GCLC Single nucleotide polymorphism Homocysteine Susceptibility |
| url | https://doi.org/10.1186/s40001-025-02688-z |
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