Susceptbility Gene And Protein Molecular Markers For Coronary Heart Disease

PART ONE The predictive value of h-FABP for myocardial ischemia and injury in perioperative period of heart surgeryObjective:To study the dynamic changes of heart-type fatty acid binding protein (h-FABP) in perioperative period of cardiac surgery, and evaluate its value in predicting myocardial ischemia and injury and relationships of h-FABP, ischemia modified albumin (IMA), cardiac troponin I (cTnI) and creatine kinase-myocardial band isoenzyme (CK-MB).Methods:We selected patients who accepted operation of coronary artery bypass graft (CABG) or ventricular septal defect repair (VSDR) from February 2008 to December 2008. Each group had 30 cases. The venous blood samples of aubjects were collected to test the levels of h-FABP, IMA, cTnI and CK-MB respectively in preoperation, aortic clamping, and 10min, 2h, 6h, 12h, 24h after aortic unclamping, respectively. Results:Changes of h-FABP and IMA levels were in consistent trend at different time points in the perioperative period. Compared with cTnI and CK-MB, h-FABP had the similar trend with them, but when the myocardial ischemia and injury occurred, h-FABP in blood had the earlier peak time, a relatively short maintain time, and declined sharply 2h later. Compared with the preoperative serum levels, after aortic unclamping 2h, h-FABP achieved the peak with earlier and much higher increased range than IMA, cTnI and CK-MB peaks. After linear correlation analysis, in CABG group, the peak value of h-FABP were positively correlated with IMA, CK-MB and cTnI (P<0.05), correlation coefficients r were 0.948, 0.964 and 0.961, respectively. The similar results were found in the VSDR group, the peak value of h-FABP were positively correlated with IMA, CK-MB and cTnI (P<0.01), correlation coefficient r were 0.986, 0.978 and 0.957, respectively.Conclusions:h-FABP is a early diagnosis index for myocardial ischemia and injury in perioperative period of cardiac surgery. Dynamically monitor h-FABP levels in blood can effectively predict the severity of myocardial ischemia and injury.PART TWO Polymorphisms analysis of 10 susceptbility gene loci of coronary heart disease in Han Chinese in south China Objective:To study the genotypes and allele frequencies of 10 single nucleotide polymorphisms (SNPs) of coronary heart disease (CHD) susceptbility genes in Han Chinese in the south.Methods:Based on the ABI prism?SNaPshot? system (minisequ -encing), 68 cases Han population in south China with non-coronary artery disease were selected from March 2008 to June 2009 to analyze the 10 SNPs genotypes and gene frequencies.Results:There were some differences of SNPs distribution frequencies between Han Chinese in south and north China in loci of rs2713604 and rs3803(x2=13.731, P<0.01 and x2=23.192, P<0.01, respectively). Compared with Japan populations (JPT) from Tokyo city, Utah's ancestors came from Europe to settle in the northern and western populations (CEU), Nigeria's Yoruba people Bataan excellent (YRI), Han Chinese in south China had the significant difference in gene frequencies in some SNPs loci. rs10757274 G/A, rs2383206A/G, rs10757278A/G and rs1333049C/G in 9p21 district analyzed in pairs showed strong linkage disequilibrium each other, its major haplotypes were GGGC and AAAG.Conclusions:There are differences in SNPs frequencie distribution in loci of rs2713604 and rs3803 between Han population in south and north China. Differences in SNPs loci of the genotype and gene frequency distribution depend on the degree of similarity of ethnic origin and the margin of geographical distance in human races. GGGC and AAAG are major haplotypes for the alleles of rs10757274G/A, rs2383206A/G, rs10757278A/G and rs1333049C/G in 9p21 district in Han Chinese in the south.PART THREE Analysis of single nucleotide polymorphisms and haplotypes of coronary heart disease susceptibility genesObjective:Study the correlation of 10 SNPs and their haplotypes in coronary heart disease (CHD) in Han Chinese in south China.Methods:Two-hundred-thirty cases of CHD patients and 230 not associated with CHD subjects in Han Chinese in south China were selected in March 2008 to June 2009. Based on the ABI prism?SNaPshot? system (minisequencing), 10 SNPs of CHD susceptibility gene and the genotypes were analyzed.Results:The results showed SNP that loci of rs10757278G in 9p21 district, HNRPUL1 gene rs11881940T and GATA2 gene rs3803T had high correlations with CHD (P<0.05). OR (95% CI) were 1.242 (1.038 to 1.487), 0.767 (0.605 to 0.973) and 0.532 (0.395 to 0.717). Logistic regression analysis showed ATC was positively correlated with blood glucose abnormalities, OR (95% CI) was 1.912 (1.012 to 3.610), P<0.05. GAT had a positive correlation with hypertension, OR (95% CI) was 2.859 (1.402 to 5.827), P<0.01.Conclusions:rs10757278G is an independent risk factor for CHD; the loci of rs11881940T and rs3803T were protective factors for the CHD. The haplotypes of ATC and GAT was positively correlated with high blood pressure and blood glucose abnormalities, separately.