| Backward:Coronary heart disease (CHD) is the most common form of cardiovascular disease. It is a complex multifactorial disease, which results from multiple genes, environmental factors and the interaction between them is still the most important worldwide morbidity and mortality reasons. There are many risk factors for coronary heart disease. More and more people pay attention to study and found risk factors from genetically for early diagnosis and treatment of coronary heart disease, and to provide a multi-faceted argument for coronary heart disease. As genes associated with endothelial system, thrombomodulin (TM) is a transmembrane glycoprotein distributed in the endothelial cell surface of veins, arteries and capillary. TM also is a thrombin receptor mainly synthesized by vascular endothelial cells and attached to an endothelial cell surface. It plays a very important role in regulating balance of blood coagulation and fibrinolysis system, thus thrombosis adjustment. Soluble thrombomodulin (sTM) is a soluble form of TM, which is a sign of vascular endothelial injury and associated with a variety of inflammatory diseases. Meanwhile, high-sensitivity C-reactive protein (hs-CRP) is an important inflammatory factor in all the inflammation factors and cytokines of the organism. It is a sensitive acute phase protein synthetized by hepatic, and a powerful inflammation marker which can predict cardiovascular risk.Objective:To explore the relevance of TM gene polymorphism and coronary heart disease, and prepare foundation of coronary heart disease’s early genetics, early diagnosis and early treatment from genetically; To study the correlation between sTM, hs-CRP plasma levels and coronary heart disease, analyze the relevance of sTM, hs-CRP plasma levels and the different range of coronary artery lesion, and estimate the diagnostic value of sTM and hs-CRP plasma levels in coronary heart disease. To do our best to provide proof multi-faceted by finding more and more possible risk factors for coronary heart disease’s early genetics, early diagnosis and early treatment.Methods:The candidate single nucleotide polymorphisms (SNPs) were screened by literature reading and biological information analysis. Subjects from department of cardiology in the first hospital of Lanzhou University were recruited by inclusion criteria and exclusion criteria from March2011to June2013. This study was based on case-control study design. DNA and plasma was extracted from the subjects’arterial blood. The gene sequencing assay of sequenom time of flight mass spectrometry was carried out to determine TM genotype distribution in control group and case group. The ELISA was carried out to determine sTM and hs-CRP plasma levels. The differences of sTM and hs-CRP plasma levels in different groups and the range of coronary artery lesion were observed. The diagnosis value of sTM and hs-CRP plasma levels for coronary heart disease was also observed.Results:4SNP were screened by literature reading and biological information analysis, including rs13306848G/A, rs1042579C/T, rs3176123A/C, rs1042580A/G. In control group and ACS group, the frequencies of GG, GA, AA type of rs13306848G/A [GG:76.2%(128/168) vs.84.1%(169/201), GA:22.6%(38/168) vs.15.4%(31/201), AA:1.2%(2/168) vs.0.5%(1/201)], CC, CT, TT type of rs1042579C/T [CC:57.7%(97/168) vs.65.2%(131/201), CT:39.3%(66/168) vs.31.3%(63/201), TT:3%(5/168) vs.3.5%(7/201)], and AA, AC, CC type of rs3176123A/C [AA:56.5%(95/168) vs.62.2%(125/201), AC:39.3%(66/168) vs.33.8%(68/201), CC:4.2%(7/168) vs.4%(8/201)] were similar between the two groups (P=0.057, P=0.143, P=0.222), there were also no statistical difference between control group and the ACS subgroups. On this basic, we random drowed some subjects and included stable angina (SAP) to study as a positive control. The three groups showed significant differences in sTM plasma levels each other[ACS group＞SAP group＞control group,(97.31±4.19)pg/ml＞(72.16±6.70)pg/ml＞(52.29±2.28)pg/ml, all P＜0.05]; The plasma levels of hs-CRP were higher in ACS group compared with control group[(2.91±0.08)ug/ml＞(2.55±0.09)ug/ml, P=0.012], there were no statistical difference among the other interblocks(all P＞0.05); There were no statistical difference between sTM, hs-CRP plasma levels and the different range of coronary artery lesion (all P＞0.05). There was no correlation between sTM and hs-CRP plasma levels(r=-0.070, P=0.116). There were statistical significant for estimating ACS by sTM and plasma levels(P＜0.001, P=0.048).Conclusions:TM rs13306848G/A, rs1042579C/T and rs3176123A/C polymorphism are not associated with acute coronary syndrome and the ACS subgroups. sTM and hs-CRP can predict the stability of coronary plaques in patients with coronary heart disease, and they may predict acute coronary syndrome, but they are not associated with the range of coronary artery lesion. |
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