1.Association between inflammatory cytokine CD40 gene polymorphism and risk of acute coronary syndrome.
Cai-Xia TIAN ; Yan LI ; Ming WANG ; Zun-En XIA ; Xiao-Yan LI ; Cong-Xin HUANG
Chinese Journal of Cardiology 2008;36(3):199-204
OBJECTIVETo 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.
RESULTSInflammatory 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).
CONCLUSIONInflammatory cytokines were increased in ACS patients and CD40-1C/T polymorphism is associated with higher risk for ACS in Han Chinese.
Acute Coronary Syndrome ; genetics ; Aged ; CD40 Antigens ; genetics ; metabolism ; CD40 Ligand ; genetics ; metabolism ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide
2.Association of L-selectin gene polymorphism with susceptibility to coronary heart disease.
Zun-en XIA ; Yan LI ; Kai-hua MING ; Xiao-quan XIONG
Chinese Journal of Medical Genetics 2007;24(2):173-176
OBJECTIVETo investigate the possible association between L-selectin gene P213S polymorphism and coronary heart disease (CHD) in Chinese population.
METHODSIn total 212 CHD patients diagnosed by angiography and 230 healthy controls were studied. The genotype and allele frequencies of L-selectin gene polymorphism were assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
RESULTSThe frequency of the L-selectin gene 213P allele in CHD patients was significantly higher than that in the control group (77.59% vs 69.35%, P=0.006). Compared with the SS genotype, PP homozygote had a significantly increased CHD risk (OR=2.70 and OR=2.15 using unadjusted and adjusted Logistic regression models, respectively). No association was found between the severity of CHD and the Lselectin gene P213S polymorphism
CONCLUSIONOur findings suggest that L-selectin gene 213P mutant allele might contribute to susceptibility of Chinese individuals to contract CHD.
Adult ; Aged ; Aged, 80 and over ; Coronary Disease ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; L-Selectin ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics