The Relationship between CD40 Gene Polymorphism and Unstable Coronary Atherosclerotic Plaques

Abstract

Background: Recently, CD40 polymorphism was found to be associated with acute coronary syndromes. However, few study was involved in the relationship between CD40 polymorphism and the risk of the vulnerable plaque to rupture so far. Materials and Methods: A total of 699 patients who have received coronary angiography were divided into 3 groups according to the morphological division of the plaques: complex lesions (343 cases), smooth lesions (131 cases), and control group (225 cases).The gene polymorphism was measured by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and identified by sequencing. Results: The CC genotype and C allele frequency of the CD40 gene in the complex lesions group is significantly higher than in the smooth lesions group and the control group (P < .001), while the TT genotype frequency in the complex lesions group is significantly lower than that of the smooth lesions group and the control group (P < .001). The C allele increased disruption risk of the plaques in the complex lesions group as compared with the smooth lesions group (odds ratio [OR]: 1.697, 95% confidence interval [CI]: 1.273-2.261). No significant differences in genotypes or allele frequencies were found between the smooth lesions group and the control group. Conclusion: Our results suggested that CD40 (−1C/T) polymorphism was associated with unstable coronary atherosclerotic plaques. The C allele frequency increased the risk of disruption of the coronary atherosclerotic plaques.

Platelet Function and Antiplatelet Therapy in Cardiovascular Disease: Implications of Genetic Polymorphisms

“…The CD40 gene (-1C/T) polymorphism has been shown to be associated with vulnerability of atherosclerotic plaques. In a cohort of Chinese patients with CVD the C allele of the gene has been associated with increased risk of plaque rupture (OR 1.7, 95%CI 1.3-2.3) [128]. However, it remains unknown whether a similar effect of these polymorphisms persist in other ethnic cohorts.…”

Genetic Variants of CD40 Gene Are Associated with Coronary Artery Disease and Blood Lipid Levels

“…Increasing evidence shows that the CD40-CD40L system plays a critical role in atherosclerotic disease progression and plaque destabilization [ 13 ]. Studies showed that polymorphisms in CD40 may influence individuals' susceptibility to the development of cardiovascular events [ 18 , 26 ]. Studies had reported the relationship between rs1883832 at CD40 locus and acute coronary syndrome [ 27 , 28 ].…”

Lymphocytic tumor necrosis factor receptor superfamily co-stimulatory molecules in the pathogenesis of atherosclerosis

“…Various studies showed that Apoe À/À /Cd40l À/À mice, as well as anti-CD40L antibody-treated Ldlr À/À or Apoe À/À develop reduced atherosclerosis and/or a plaque phenotype that shows a reduction in inflammation, reminiscent of stable atherosclerotic plaques in humans [18][19][20][21][22][23][24][25][26][27][28][29][30]. The effect of CD40L on atherosclerosis appeared hematopoietic cell-independent, as shown by Cd40l…”

“…Platelet CD40L is atherogenic, and plays a major role in platelet-leukocyte aggregation and leukocyte recruitment to the endothelium [16]. Expression of CD40(L) in atherosclerotic lesion [22] Increased levels of sCD40L in patients with unstable angina [23] Polymorphisms in CD40 gene correlate with unstable coronary plaques and risk of coronary plaque disruption [24] CD137L CD137 Atherogenic -shown by administration of agonistic antibody against CD137L and Cd137 genetically deficient mice [23,25] Expression of CD137 in atherosclerotic lesion [25] Increased sCD137 levels in patients with ACS [26,27] CD70 CD27 Atherogenic -shown by reduced atherosclerosis in Cd70 À Apoe transgenic mice [28] Expression of CD70 and CD27 on T cells in atherosclerotic lesions [29] OX40L OX40 Atherogenic -shown by administration of neutralizing antibodies to OX40 and Ox40l genetically deficient mice [30,31,32] Increased expression of OX40 in patients with unstable angina…”

“…Polymorphisms in the CD40 gene (-1C/T) correlate with unstable coronary plaques, whereas the C allele frequency increased risk of coronary plaque disruption in 699 patients [24]. Moreover, several studies showed that sCD40L in the circulation is highly correlated with cardiovascular risk in humans, but its biological function remains to be elucidated until today [23,56,57].…”