| Objective Research on the distribution characteristics of lipoprotein-associated phospholipase A2(Lp-PLA2) gene A379 V and T403 C polymorphisms in Fujian Han population and its relationship with coronary heart disease, and to explore the role of Lp-PLA2 gene polymorphism in the pathogenesis of coronary heart disease(CHD).And through detecting the levels of Lp-PLA2 in patients with CHD, we analysis its relationship between coronary atherosclerotic plaque stability and coronary artery lesions to explore the predictive value of Lp-PLA2 levels to the CHD.Methods(1) Research Group by case-control study, including 160 cases of patients with CHD and 117 cases of healthy control subjects, which 160 cases of patients with CHD according to the different standard divided into different subgroups:(1) divided into no stable angina pectoris(UAP) group and acute myocardial infarction(AMI)group according to the clinical types of CHD;(2)divided into single vessel lesion group,double vessel lesions group and multi vessel lesion group according to the number of diseased coronary arteries;(3) divided into mild stenosis group, moderate stenosis group and severe stenosis group according to the degree of coronary artery stenosis and the Gensini integral.(2) By gene sequencing technology to detect two single nucleotide polymorphism sites of Lp-PLA2 gene A379 V and T403 C of all subjects; by enzyme linked immunosorbent assay was used to measure the levels of plasma Lp-PLA2.Immunofluorescence method was used to determination of plasma hs- c Tn I levels.Result(1) the mean HDLC levels in CHD group was significantly lower than healthy control group, while age,the proportion of male sex, hs- c Tn I and hs- CRP, TC, LDL-C,Lp(a), WBC, MO and Lp-PLA2 were significantly higher than healthy control group(P﹤0.01). The levels of TG and Apo B between two groups were no significant difference(P﹥0.05).(2) The A379 V site was detected CC, CT, TT of three genotypes, The T403 C site was detected TT, TC, CC of three genotypes.(3) Compared to the control group, the frequencies of CC genotype and C allele were increased in CHD group(P ﹤ 0.05).Multivariate logistic regression analysis showed that CC genotype was an independent risk factor for CHD, whereas A379 V distribution was no significant difference in two groups(P﹥ 0.05). Haplotype analysis showed that the GC haplotype was associated with the risk of CHD.(OR=1.928,95%Cl:1.174-3.167,P=0.009).(4) The frequencies of the two sites in the same sex were the same, all of which were CC﹥CT+TT and TT﹥TC+CC, the genotype distribution was no significant difference among the patients with different sex of CHD(P﹥0.05).The frequenies of CT+TT and TC+CC were higher than single group(88.5% vs 11.5%, 62.0%vs38.0%)(P﹤0.05).The genotype distribution of the two locus in both single and multi vessel disease groups were differences. The Gensini scores of CT+TT and TC+CC were higher than CC and TT genotypes(47.71 +15.65vs42.18 + 18.62. 46.81 + 16.34vs43.32 + 19.12)(all P﹤0.05),and A379 V and T403 C mutation may be related to the severity of coronary artery disease.(5) The level of Apo B in CHD patients with CT+TT genotype was higher than CC genotype(4.72 +18.42 vs 0.32 + 0.98, P﹤0.01). The plasma Lp-PLA2 level in CHD was significantly higher than healthy control group(248.59 + 76.51 vs 49.41 + 119.98, P﹤0.01).(6) The plasma Lp-PLA2 levels were significant differences between the groups.: AMI group﹥UAP group ﹥ healthy control group(276.73 + 69.09 vs 119.98 + 70.53 vs 213.32 +49.41, all P﹤0.001).(7) The levels of plasma Lp-PLA2 were 204.21 + 83.16, 229.83 +64.19 and 291.61 + 57.37ng/m L in single vessel disease group, double vessel disease group and multiple vessel disease group respectively; which in healthy control group was 116.92±50.13 ng / m L, the levels of Lp-PLA2 were different between four subgroups, we found that with the number of diseased coronary branches increased,the levels of Lp-PLA2 raised, the difference was statistically significant(P﹤0.01).(8) The Lp-PLA2 levels were significantly different between the healthy control group, mild,moderate and severe stenosis group. The levels of Lp-PLA2 were 116.92±50.13, 147.47+ 50.99, 233.21 + 75.03, 277.10 + 59.22 respectively. Using SNK statistical methods,the levels of Lp-PLA2 had no difference between the healthy control group and the mild stenosis group(P﹥0.05), there were significant differences among the other groups(P﹤ 0.01).(9) The receiver operating characteristic curve( ROC) showed that the efficiency of hs-c Tn I, Lp-PLA2 and their combination were higher in the prediction of CHD. The area under curve(AUC) was maximum when they combined, hs-c Tn I was second, Lp-PLA2 was minimum,the AUC of hs-c Tn I+Lp-PLA2, hs-c Tn I and Lp-PLA2 in the prediction of CHD were 0.842, 0.727 and 0.713 respectively(all P﹤0.05). The sensitivity were 84.2%, 86.3% and 67.4%,and the relative specificity were 78.6%,68.5%, 89.5%, respectively.Conclusion(1) Lp-PLA2 gene T403 C polymorphism was associated with the risk of CHD in Fujian Han population, the frequencies of the CC genotype and C allele were higher in CHD patients than normal controls, the CC genotype is an independent risk factor for CHD.Lp-PLA2 gene mutations were associated with the severity of coronary artery disease, it may be a genetic factor in the pathogenesis of CHD.(2) The level of plasma Lp-PLA2 may be associated with the risk of CHD,it can reflect the stability of atherosclerotic plaque and coronary artery lesions and the degree of stenosis and also can predict the occurrence of CHD, especially when it combine with hs-c Tn I,they can accurately improve prediction. |
