A common polymorphism in CD40 Kozak sequence (-1C/T) is associated with acute coronary syndrome

Objective

Evidence suggests the CD40-CD40L pathway as a key process in the development, progression, and outcome of acute coronary syndrome (ACS). We hypothesized that the -1C/T polymorphism of the CD40 gene would be associated with ACS and influence the CD40 expression.

Methods

The genotype distribution and allele frequency of CD40-1C/T polymorphism in 248 ACS patients and 206 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Monocytes from 90 healthy volunteers were incubated with IFN-γ. CD40 expression was detected by flow cytometry.

Result

Patients with ACS showed a significant increase of CD40 expression compared with controls (P < 0.001). The frequency of the CC genotype in the ACS group was significantly higher than that of the controls (P < 0.001). Frequency of the C allele was higher among ACS patients compared with controls (P < 0.001). Case control association analysis of the CD40 -1C/T SNP showed an association between the C allele and ACS (OR = 1.991, 95%CI: 1.526 ∼ 2.596, P < 0.001). -1C/C carriers presented significantly higher CD40 expression levels than -1C/T and -1T/T subjects, both in ACS group and controls (P < 0.001). When stimulated by IFN-γ, CD40 expression levels on monocytes in individuals with CC, CT and TT genotypes were increased by 9.16, 3.83 and 1.53 fold, respectively, compared with the levels absent with IFN-γ.

Conclusions

These results suggest that the -1C allele of the CD40 (-1C/T) gene polymorphism is a genetic factor that may determine an individual's susceptibility by ACS in Chinese. The CD40 -1C/T polymorphism is a novel regulator of CD40 expression.