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[Association between inflammatory cytokine CD40 gene polymorphism and risk of acute coronary syndrome]
Cai-Xia Tian1, Yan Li, Ming Wang
1Department of Clinical Laboratory Science, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Insights
Elevated inflammatory markers and a specific CD40 gene variant (CD40-1C/T polymorphism) are linked to increased acute coronary syndrome (ACS) risk in Han Chinese individuals. Fluvastatin demonstrated potential in inhibiting IFN-gamma-induced CD40 expression in peripheral blood mononuclear cells.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Genetics
Background:
- Acute coronary syndrome (ACS) involves complex inflammatory processes.
- CD40 signaling pathways play a role in cardiovascular disease pathogenesis.
- Genetic variations may influence susceptibility to ACS.
Purpose of the Study:
- To assess inflammatory markers (CD40, sCD40L, hs-CRP, WBC) in ACS patients.
- To investigate the association of CD40-1C/T polymorphism with ACS risk in Han Chinese.
- To examine the regulatory effects of IFN-gamma and fluvastatin on CD40 expression in PBMNCs.
Main Methods:
- Recruited 160 ACS patients and 92 controls.
- Utilized ELISA, immunoturbidimetric assay, and flow cytometry for marker detection.
- Analyzed CD40 genotype via PCR-RFLP and DNA sequencing.
- Cultured PBMNCs with IFN-gamma and fluvastatin to assess CD40 expression.
Main Results:
- ACS patients exhibited significantly higher CD40, sCD40L, hs-CRP, and WBC levels.
- The CD40-1C allele and CC genotype were associated with increased ACS risk (OR=1.608).
- IFN-gamma upregulated CD40 expression in PBMNCs, which was inhibited by fluvastatin across genotypes.
Conclusions:
- Elevated inflammatory cytokines are present in ACS patients.
- CD40-1C/T polymorphism is a risk factor for ACS in the Han Chinese population.
- IFN-gamma enhances PBMNC CD40 expression, and fluvastatin can inhibit this effect.
Objective:
To investigate the expression levels of CD40, sCD40L, hs-CRP, WBC in acute coronary syndrome (ACS) patients and the association between CD40-1C/T single nucleotide polymorphism and risk of ACS in Han Chinese, moreover, the regulatory effects of IFN-gamma and fluvastatin on the expression of CD40 in peripheral blood mononuclear cell (PBMNC) were also observed.
Methods:
(1) 160 ACS patients and 92 control patients diagnosed by coronary angiography were recruited. Enzyme linked immunosorbent assay, particle enhanced immunoturbidimetric assay, flow cytometry were used to detect the levels of soluble CD40L, hs-CRP, and WBC count. (2) The CD40 genotype and allele frequency were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing technology. (3) PBMNC were separated by density gradient centrifugation heparinized venous blood from 40 ACS patients, cultured for 24 h with or without 100 ng/ml IFN-gamma in the absence or present of 10 micromol/L fluvastatin. The CD40 expression levels were then detected by flow cytometry.
Results:
Inflammatory cytokine CD40, sCD40L, hs-CRP levels were significantly higher in ACS patients than in controls. The CD40-1C allele frequency was 0.606 in ACS group and 0.489 in controls, while T allele frequency was 0.394 in ACS group and 0.511 in controls. The frequency of CC genotype was significantly higher in ACS group than in controls (P < 0.01). C allele carriers had significantly higher risk of ACS (OR = 1.608, 95%CI: 1.12 - 2.32, P = 0.011). CD40 production increased after 24 h culturing and the CD40 levels were significantly higher in subjects with CC genotype than that in subjects with CT or TT genotype [CC: (14.78 +/- 4.56) MFI, CT: (11.98 +/- 4.12) MFI, TT: (9.86 +/- 3.83) MFI, P < 0.05]. IFN-gamma further increased PBMNC CD40 expressions in all subjects after culturing for 24 h and fluvastatin equally inhibited IFN-gamma induced PBMNC CD40 expression from various genotypes (CC, CT, TT was 30.3%, 26.3%, 29.3% respectively, all P > 0.05).
Conclusion:
Inflammatory cytokines were increased in ACS patients and CD40-1C/T polymorphism is associated with higher risk for ACS in Han Chinese.
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