Genetic Correlation Between Fibrinogen Alpha Chain Gene Polymorphism And Phlegm And Blood Stasis Syndrome Of Ischemic Stroke And Coronary Heart Disease

Objective:The purpose of this study was to investigate the correlation between the polymorphisms of fibrinogen chain gene（FGA）rs2070022,rs2070025,rs2070011 and their genetic susceptibility to ischemic stroke（IS）and coronary heart disease（CHD）phlegm and stasis syndrome,as well as the association with the quantitative traits related to the phlegm and stasis syndrome of ischemic stroke and coronary heart disease.Methods:A case-control study was conducted in this study,which included 550 cases of patients with phase-stasis syndrome of ischemic stroke,phase-stasis syndrome of coronary heart disease and the control group respectively.The genotyping was conducted with MassARRAY SNP technology.Using HITACHI HITACHI 7600 automatic biochemical analyzer,uric acid（UA）,c-reactive protein（CRP）,homocysteine（Hcy）,and blood lipid of serum level,mindray 6900 automatic blood cell analyzer were used to detect the levels of whole blood platelet,using French StAgO Capact instrument detection in plasma coagulation function indexes of coagulation.PLINK and SPSS software were used for statistical analysis.Results:1.The genotype distributions of FGA genes rs2070022,rs2070025 and rs2070011 in the control group were in accordance with the Hardy-Weinberg Equilibrium（HWE）law（all P>0.050）.2.Correlation analysis of FGA gene polymorphism with genetic susceptibility to phase-stasis syndrome of ischemic stroke and phase-stasis syndrome of coronary heart disease:There was no statistically significant correlation between the three sites of FGA gene rs2070022,rs2070025,rs2070011 and the susceptibility to phase-stasis syndrome of ischemic stroke and phase-stasis syndrome of coronary heart disease（all P>0.050）.Further gender stratification analysis revealed that among males,there was a statistical significance between rs2070011 and CHD with phlegm and blood stasis syndrome(dominant model:P_adj=0.030).3.Correlation analysis of FGA gene polymorphism with phase-stasis syndrome of ischemic stroke and phlegm and phase-stasis syndrome of coronary heart disease（1）In the total sample population,the FIB(additive model:P_adj=0.036;Dominant model:P_adj=0.026),rs2070011 was correlated with the level of FIB(dominant model:P_adj=0.034)and PLT(recessive model:P_adj=0.017)in phase-stasis syndrome of IS.（2）In men,rs2070022 loci and PLT of IS in patients with phlegm and blood stasis syndrome(dominant model:P_adj=0.039)leels,rs2070011 loci and CHD in patients with phlegm and blood stasis syndrome of APTT(dominant model:P_adj=0.031),the level of TT(dominant model:P_adj=0.038),rs2070025 loci and CHD in patients with phlegm and blood stasis syndrome of INR(recessive model:P_adj=0.031),the level of PTA(recessive model:P_adj=0.036).（3）In women,rs2070011 is associated with FIB(dominant model:P_adj=0.020)levels in patients with phase-stasis syndrome of IS.4.Correlation analysis of FGA gene polymorphism with blood pressure level of phase-stasis syndrome of ischemic stroke and phase-stasis syndrome of Coronary heart disease（1）In the total sample population,rs2070011 was associated with DBP(recessive model:P_adj=0.044)of IS with phlegm and blood stasis syndrome,and rs2070022 was associated with DBP of CHD with phlegm and blood stasis syndrome(additive model:P_adj=0.016;Dominant model:P_adj=0.034),rs2070011 is correlated with DBP(recessive model:P_adj=0.009)level of CHD phlegm and blood stasis syndrome.（2）Among males,rs2070011 was associated with DBP(recessive model:P_adj=0.044)in patients with ischemic stroke and phlegm and blood stasis syndrome,while rs2070022 was associated with DBP in patients with CHD and phlegm and blood stasis syndrome(additive model:P_adj=0.03;dominant model:P_adj=0.049)horizontal correlation.（3）In women,rs2070011 was associated with DBP in patients with CHD and phlegm and blood stasis syndrome(additive model:P_adj=0.014;dominant model:P_adj=0.000).5.Correlation analysis of FGA gene polymorphism with blood glucose level of phase-stasis syndrome of ischemic stroke and phase-stasis syndrome of coronary heart disease（1）In the total sample population,rs2070022 was associated with FPG in patients with IS and phlegm and blood stasis syndrome(additive model:P_adj=0.028;dominant model:P_adj=0.027).（2）In men,rs2070025 is associated with FPG(recessive model:P_adj=0.042)levels in CHD patients with phlegm and blood stasis syndrome.（3）In women,rs2070025 is associated with FPG(recessive model:P_adj=0.015)levels in patients with IS with phlegm stasis syndrome.6.Correlation analysis of FGA gene polymorphism with phase-stasis syndrome of ischemic stroke and phase-stasis syndrome of coronary heart disease（1）In the total sample,rs2070022 site correlated with the levels of APO-A(additive model:P_adj=0.003;Dominant model:P_adj=0.006),HDL(additive model:P_adj=0.038)of IS phlegm and blood stasis syndrome;Recessive model:P_adj=0.032)level correlated,rs2070011 site correlated with the levels of APO-A(dominant model:P_adj=0.027)and APO-B(dominant model:P_adj=0.046)of CHD phlegm and blood stasis syndrome,and rs2070022 site correlated with the levels of HDL(dominant model:P_adj=0.003)of CHD.（2）Among males,the rs2070022 site is related to APO-A(additive model:P_adj=0.014;dominant model:P_adj=0.031)and HDL(additive model:P_adj=0.023)of patients with IS with phlegm and blood stasis syndrome.The rs2070011 site is related to APO-B(dominant model:P_adj=0.045)and TC(additive model:P_adj=0.021)of patients with IS with phlegm and blood stasis syndrome.The dominant model:P_adj=0.003)level was correlated,and the rs2070011 site was correlated with the level of APO-A(dominant model:P_adj=0.019)in patients with CHD phlegm and blood stasis syndrome.（3）In women,rs2070011 was associated with phase-stasis syndrome of IS of TG(dominant model:P_adj=0.002),rs2070011 was associated with phase-stasis syndrome of CHD of APO-A(recessive model:P_adj=0.043),and rs2070022 was associated with HDL(additive model:P_adj=0.014;Dominant model:P_adj=0.010)in patients with phase-stasis syndrome of CHD.7.Correlation analysis of FGA gene polymorphism with the levels of c-reactive protein,homocysteine and uric acid in the phlegm and blood stasis syndrome of ischemic stroke and the phlegm and blood stasis syndrome of coronary heart disease（1）In the total sample,the three polymorphic loci of FGA,rs2070022,rs2070025 and rs2070011,were not correlated with the levels of CRP,Hcy and UA in patients with phase-stasis syndrome of ischemic stroke and phase-stasis syndrome of coronary heart disease（all P>0.050）.（2）In men,rs2070022 is associated with Hcy(recessive model:P_adj=0.012)in patients with phase-stasis syndrome of ischemic stroke.（3）In women,rs2070025 is associated with UA(additive model:P_adj=0.021;Dominant model:P_adj=0.014)in patients with phase-stasis syndrome of CHD.Conclusion:Polymorphisms of FGA genes rs2070022,rs2070025 and rs2070011 are not related to the susceptibility of phlegm and blood stasis syndrome of ischemic stroke and coronary heart disease,while rs2070011polymorphisms are associated with male coronary heart disease and phlegm and blood stasis syndrome.rs2070022,rs2070025 and rs2070011polymorphisms may affect the coagulation function of phlegm and blood stasis syndrome in ischemic stroke,while rs2070025 and rs2070011polymorphisms may affect the coagulation function of CHD phlegm and blood stasis syndrome.rs2070011 polymorphism may affect the blood pressure level of phlegm and blood stasis syndrome in ischemic stroke,rs2070022 and rs2070011 polymorphism may affect the blood pressure level of CHD phlegm and blood stasis syndrome.rs2070022 and rs2070025 polymorphism may affect the blood glucose level of the phlegm and blood stasis syndrome in ischemic stroke,and rs2070025polymorphism may affect the blood glucose level of the phlegm and blood stasis syndrome in coronary heart disease.rs2070022 and rs2070011 polymorphisms may affect the level of blood lipid in ischemic stroke and coronary heart disease.