Association between ADAM17 promoter polymorphisms and ischemic stroke in a Chinese population.

ABSTRACT

AIM: Stroke is a leading cause of death and disability worldwide. Most ischemic strokes (IS) are caused by atherosclerosis. Recently, the pivotal role of ADAM17 in atherosclerosis has been thoroughly addressed. However, the association between ADAM17 and IS has not yet been thoroughly explored. The present study therefore aimed to investigate the association between disintegrin and metalloproteinase 17 (ADAM17) gene polymorphisms and the risk of ischemic stroke (IS). METHODS: The associations between five ADAM17 promoter polymorphisms and the risk of IS were assessed in 342 patients with IS and 296 age-matched healthy individuals in a case-control study. RESULTS: The allele and genotype frequencies of the ADAM17 polymorphisms (rs11684747, rs11689958, rs12692386, rs55790676 and rs1524668) did not differ significantly between the IS patients and healthy control group subjects. In addition, no significant associations were detected between the ADAM17 haplotypes and IS. The mean intima-media thickness in the IS patients was not associated with the ADAM17 polymorphisms. When the IS patients were stratified according to their OCSP classification, the genotype frequencies of the ADAM17-rs1524668 polymorphism exhibited a significant association with the PACI subtype of IS. Moreover, the ADAM17-rs12692386 A＞G polymorphism was found to be associated with a higher ADAM17 mRNA expression. CONCLUSIONS: The SNPs in the ADAM17 promoter region do not appear to be major contributors to the pathogenesis of IS. However, the rs12692386 G ADAM17 allele is correlated with a higher expression of ADAM17 mRNA, which may play a role in increasing inflammation in IS patients. Furthermore, the ADAM17-rs1524668 polymorphism is linked to a higher risk of PACI-type stroke, confirming the role of ADAM17 in the pathophysiology of PACI, with potentially important therapeutic implications.