Association Study Of TP53 Polymorphism And Phlegm-blood Stasis Syndrome Of Ischemic Stroke And Coronary Heart Disease

Objective:The purpose of this study was to investigate the association of tumor protein p53?TP53?polymorphisms with the mRNA expression and related clinical indexes of phlegm stasis syndrome in ischemic stroke?IS?and coronary heart disease?CHD?.Methods:There were 550 cases of phlegm-blood stasis syndrome in ischemic stroke,550 cases of phlegm-blood stasis syndrome in coronary heart disease and 550 cases in control group.QRT-PCR was used to detect the expression of TP53 gene mRNA in the peripheral blood of patients with IS phlegm-blood stasis syndrome and CHD phlegm-blood stasis syndrome.The genotyping of TP53 gene rs4968187 and rs2287497 was carried out by using Sequenom Mass ARRAY i PLEX.Coagulation method was used to detect the blood coagulation function indexes in the plasma of the patients with IS phlegm-blood stasis syndrome and CHD phlegm-blood stasis syndrome,and Hitachi7600 automatic biochemical analyzer was used to detect the blood lipid related indexes of phlegm-blood stasis syndrome with IS and CHD according to the standardized experimental procedure.Statistical analysis was done by PLINK and SPSS software.Results:1.Comparison of TP53 mRNA expression level in phlegm-blood stasis syndrome with IS and CHD and controlThe expression level of TP53 gene mRNA in patients with is phlegm stasis syndrome was significantly lower than that in the control group?P<0.001?,and CHD patients exhibited a lower TP53 expression level than controls?P=0.010?.2.Hardy Weinberg equilibrium?HWE?test:the genotype frequencies of rs4968187?P=0.821?and rs2287497?P=0.295?were in HWE in the control group.3.Genotype frequency distribution?1?There was no significant difference in the distribution frequency of rs4968187 and rs2287497 polymorphisms of TP53 gene between IS and CHD?P>0.050?;?2?In the gender stratification analysis,the rs4968187 and rs2287497 had no significant difference in the distribution frequency between the male or female is phlegm stasis syndrome and CHD phlegm stasis syndrome group and the control group?P>0.050?.4.The association analysis of TP53 gene polymorphisms with the genetic susceptibility of phlegm-blood stasis syndrome with IS and CHD?1?In each genetic model,rs4968187 and rs2287497 polymorphisms of TP53gene had no significant correlation with the genetic susceptibility of phlegm-blood stasis syndrome with IS and CHD?P>0.050?.?2?In gender stratification analysis,no significant correlation between rs4968187 and rs2287497 with the genetic susceptibility of phlegm-blood stasis syndrome with IS and CHD?P>0.050?.5.The association analysis of rs4968187,rs2287497 and clinical indexes of IS patients with phlegm and blood stasis syndrome?1?The correlation between rs2287497 andmodel:P_adj=0.025;Dominant model:P_adj=0.006)in male patients with IS phlegm-blood stasis syndrome was statistically significant.There were significant difference between rs2287497 and APTT(Recessive model:P_adj=0.025)and PTA(Recessive model:P_adj=0.026)levels in male patients with IS phlegm-blood stasis syndrome.Significant difference also found between rs2287497 and UA(Additive model:P_adj=0.030;Dominant model:P_adj=0.004)level in male patients with IS phlegm-blood stasis syndrome.?2?Rs4968187 variants of TP53 gene was significantly correlated with FPG(Additive model:P_adj<0.001;Dominant model:P_adj=0.006;Recessive model:P_adj<0.001),P2h PG(Additive model:P_adj<0.001;Dominant model:P_adj=0.008;Recessive model:P_adj<0.001)level of the patients with IS phlegm-blood stasis syndrome,and with the TC level of the male patients with IS phlegm-blood stasismodel:P_adj=0.037).6.Association analysis of rs4968187 and rs2287497 with clinical indexes of CHD patients with phlegm stasis syndrome?1?The correlation between rs2287497 and SBP in female patients with CHD phlegm-blood stasis syndrome was statistically significant(Dominant model:P_adj=0.014),and with the INR(Recessive model:P_adj=0.023)and PT(Recessive model:P_adj=0.012)levels in CHD patients with phlegm-blood stasis syndrome.Rs2287497 was significantly correlated with APTT(Additive model:P_adj=0.041)?PT(Recessive model:P_adj=0.009)and TT(Additive model:P_adj=0.022;Recessive model:P_adj=0.010)levels in male patients with CHD phlegm-blood stasis syndrome,and also correlated with INR(Recessive model:P_adj=0.025)levels in CHD patients with phlegm-blood stasis syndrome.At the same time,the rs2287497 was also statistically related to the HDL?both P<0.050?levels of the total population(Recessive model:P_adj=0.005)and female patients(Additive model:P_adj=0.006;Recessive model:P_adj=0.000)of CHD phlegm-blood stasis syndrome,and with Hcy(Additive model:P_adj=0.032;Recessive model:P_adj=0.002)level in CHD patients with phlegm-blood stasis syndrome.?2?Rs4968187 polymorphism is related to blood pressure level in CHD patients with phlegm-blood stasis syndrome(Additive model:P_adj=0.023;Dominant model:P_adj=0.028).The correlation between rs4968187polymorphism and TG(Additive model:P_adj=0.023;Dominant model:P_adj=0.010)in female patients with CHD phlegm-blood stasis syndrome was statistically significant.Conclusions:1.The expression level of TP53 gene may be related to the occurrence of IS phlegm-blood stasis syndrome and CHD phlegm-blood stasis syndrome,TP53 gene may be a shared risk gene of the two diseases.2.The rs2287497 polymorphism of TP53 gene may affect the coagulation function of IS phlegm-blood stasis syndrome and CHD phlegm-blood stasis syndrome at the same time,and it may be a risk gene variant for coagulation function of both diseases.