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Genetic predisposition to ischaemic stroke by RAGE and HMGB1 gene variants in Chinese Han population

2017; Impact Journals LLC; Volume: 8; Issue: 59 Linguagem: Inglês

10.18632/oncotarget.22112

1949-2553

You Li, Jing Zhu, Linfa Chen, Weidong Hu, Mengxu Wang, Shengnan Li, Xuefeng Gu, Hua Tao, Bin Zhao, Guoda Ma, Keshen Li,

Parkinson's Disease Mechanisms and Treatments

// You Li 1, 3, * , Jing Zhu 2, * , Linfa Chen 2 , Weidong Hu 2 , Mengxu Wang 2 , Shengnan Li 1 , Xuefeng Gu 1 , Hua Tao 1 , Bin Zhao 1 , Guoda Ma 1 and Keshen Li 1, 3 1 Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China 2 Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China 3 Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China * These authors have contributed equally to this work Correspondence to: Guoda Ma, email: sihan1107@126.com Keshen Li, email: keshenli1971@163.com Keywords: RAGE ; HMGB1 ; ischaemic stroke; gene variants; case-control study Received: June 22, 2017     Accepted: September 20, 2017     Published: October 26, 2017 ABSTRACT Emerging evidence suggests that the multiligand receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 protein (HMGB1) contribute to the pathophysiology of ischaemic stroke (IS). The present study aimed to investigate the association of RAGE and HMGB1 variants with the risk of IS. A total of 1,034 patients and 1,015 age- and sex-matched healthy controls were genotyped to detect five genetic variants of the RAGE gene and four genetic variants of the HMGB1 gene using the Multiplex SNaPshot assay. We found that the rs2070600 variant of RAGE was associated with an increased risk of IS (OR = 1.19, 95% CI: 1.02-1.38, P = 0.043), whereas the rs2249825 variant of HMGB1 was associated with a decreased risk of IS (OR = 0.83, 95% CI: 0.71-0.98, P = 0.041). Further stratification by IS subtypes revealed that the presence of the TT genotype of the RAGE rs2070600 variant confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.036). Moreover, patients with the variant T allele of the RAGE rs2070600 variant presented with reduced serum soluble RAGE production. Patients carrying the variant G allele of the HMGB1 rs2249825 variant exhibited significantly lower infarct volumes than those with the major CC genotype. These clues may help in the development of optimal personalized therapeutic approaches for IS patients.