Single nucleotide polymorphism of CD40 in the 5'-untranslated region is associated with ischemic stroke

Abstract

Objectives: Ischemic stroke is influenced by both environmental and genetic factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic responses, which are involved in the pathophysiology of ischemic stroke. The aim of this study was to evaluate association between the CD40 -1C/T single nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.

Methods: We conducted a case-control study including 286 ischemic stroke patients and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, and evaluated its relevance to ischemic stroke susceptibility.

Results: Significantly increased ischemic stroke risk was found to be associated with the T allele of CD40 -1C/T (OR=1.273, 95% CI=1.016-1.594). The frequencies of CT and TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly higher than those of controls, respectively (for CT: OR=2.350, 95% CI=1.601-3.449; for TT/CT: OR=2.148, 95% CI=1.479-3.119). And, similar results were obtained after adjusting non-matched variables. We found that the frequency of carried T genotypes (TT and TT/CT) was significantly increased in patients with history of stroke compared with patients without (for TT: OR=6.538, 95%CI=1.655-25.833; for TT/CT: OR=3.469, 95%CI=1.031-11.670), respectively.

Conclusions: The findings suggested that the CD40 -1C/T polymorphism might contribute to the susceptibility to ischemic stroke in the Chinese population, and might be associated with history of previous stroke.

Keywords: 5′-UTR; 5′-untranslated region; CD40; CD40 ligand; CD40L; CE; CHD; CI; CNS; CT; Genetic susceptibility; HWE; Hardy–Weinberg equilibrium; ICD-9-CM; International Classification of Diseases, 9th Revision, Clinical Modification; Ischemic stroke; LAA; LD; MRI; NIHSS; National Institutes of Health Stroke Scale; OR; PCR-RFLP; SNP; SVO; Single nucleotide polymorphism; TNFR; TOAST; Trial of Org10172 in Acute Stroke Treatment; cardioembolism; central nervous system; computed tomography; confidence intervals; coronary heart disease; large artery atherosclerosis; linkage disequilibrium; magnetic resonance imaging; odds ratio; polymerase chain reaction-restriction fragment length polymorphism; sCD40; single nucleotide polymorphism; small vessel occlusion; soluble CD40; tumor necrosis factor receptor.