Association Between JAK2 And STAT3 Gene Polymorphisms And Susceptibility To With Risk Of Ischemic Stroke With Phlegm And Blood Stasis And Coronary Heart Disease With Phlegm And Blood Stasis

Objective:The Janus kinase?JAK?/signal transducer and activator of transcription?STAT?signaling pathway is critical for regulating the stress responses of the heart and the brain to various insults.This study was aimed to explore the association between JAK2 gene polymorphisms rs1887429,rs2274472,STAT3 gene polymorphisms rs4796793 with risk of ischemic stroke?IS?with phlegm and blood stasis syndrome and coronary heart disease with phlegm and blood stasis syndrome and and the related quantitative traits.Methods:We recruited 550 IS patients with phlegm and blood stasis syndrome,550 CHD patients with phlegm and blood stasis syndrome,and 550 gender-and age-matched controls.The genotyping was conducted on the Agena platform.A Hitachi 7600 automatic biochemical analyzer?Japan?was used to detect the serum levels of the lipids,which included apolipoprotein A,apolipoprotein B,high-density lipoprotein,low-density lipoprotein,triglyceride,and total cholesterol.The plasma levels of the coagulation function index,were measured according to the solidification method using a StAgO compact fully automatic blood coagulation analyzer?France?.SPSS 16.0 for Windows and PLINK software?http://pngu.mgh.harvard.edu/^purcell/plink/?was used for genetic association analysis.Results:1.Hardy-Weinberg Equilibrium?HWE?test:?1?the genotype frequencies of rs1887429 and rs2274472 were in HWE in the control group,as well as the male or female control group?all P>0.050?.?2?No significant difference was found in the genotype distributions of rs1887429,rs2274472 and rs4796793 between CHD with phlegm and blood stasis syndrome or IS with phlegm and blood stasis syndrome and the controls?all P>0.050?.In the gender stratification analysis,a significant difference in the genotype distributions of rs1887429 and rs2274472 between the female CHD with phlegm and blood stasis and female control groups was observed?P=0.037 and P=0.005,respectively?.2.Association of JAK2 and STAT3 gene polymorphisms with IS with phlegm and blood stasis risk?1?Rs1887429,rs2274472,and rs4796793 were not significantly associated with risk of IS with phlegm and blood stasis syndrome?all P>0.050?;?2?After gender-specific stratification analysis,statistical associations were observed between rs2274472(dominant model:P=0.016 and P_adj=0.016)and the elevated risk of female patients with IS.Rs1887429and rs4796793were not statistically significantly associated with risk of IS with phlegm and blood stasis syndrome?all P>0.050?.3.Association of JAK2 and STAT3 gene polymorphism with CHD with phlegm and blood stasis risk?1?Rs1887429,rs2274472,and rs4796793 were not statistically significantly associated with risk of CHD with phlegm and blood stasis syndromeunder?all P>0.050?;?2?After gender-specific stratification analysis,statistical associations were observed among female CHD with phlegm and blood stasis between rs1887429?additive model:P=0.016 and dominant model:P=0.011?or rs2274472?dominant model:P=0.048?and elevated CHD with phlegm and blood stasis risk.This association remained in the additive and dominant models of rs1887429 after adjusting by age(P_adj=0.012 and P_adj=0.010,respectively)but not in the dominant model of rs2274472(P_adj=0.087).4.Association between JAK2 and STAT3 gene polymorphism and serum lipid level of IS with phlegm and blood stasis syndrome?1?Rs2274472 was associated with VLDL level of IS with phlegm and blood stasis syndrome(P_adj=0.037);rs1887429,rs4796793 was not associated with serum lipid?APO-A,APO-B,HDL-C,LDL-C,VLDL,TC and TG?levle of IS with phlegm and blood stasis syndrome(P_adj>0.05).?2?After gender-specific stratification analysis,rs2274472 was associated with VLDL of male IS with phlegm and blood stasis syndrome(P_adj=0.047);No significant differences were observed in the association between rs1887429,rs4796793 and the serum lipid levels of male IS phlegm and blood stasis syndrome patients(P_adj>0.05).In the female IS with phlegm and blood stasis syndrome patients group,rs1887429?rs2274472 was not associated with serum lipid levels(P_adj>0.05);while rs4796793 was associated with HDL-C,LDL-C level(P_adj<0.050).5.Association between JAK2 and STAT3 polymorphshim and serum lipid of CHD with phlegm and blood stasis syndrome patients?1?Significant association was found between rs1887429 and HDL-C,LDL-C level of CHD with phlegm and blood stasis syndrome(P_adj<0.050).Rs2274472 was siginificantly associated with APO-B level of CHD with phlegm and blood stasis syndrome(P_adj=0.025).No Significant association was found between rs4796793 and serum lipid level of CHD with phlegm and blood stasis syndrome(P_adj>0.05).?2?Aftergender-specificstratificationanalysis,significant association was found between rs1887429 and LDL-C of male CHD with phlegm and blood stasis syndrome(P_adj<0.050);while,rs2274472,rs4796793 were not associated with serum lipid level of male CHD with phlegm and blood stasis syndrome(P_adj>0.05).In the female CHD with phlegm and blood stasis syndrome,significant association were found between rs1887429 and APO-A,HDL-C,LDL-C and TC level(P_adj<0.050).Rs2274472 was associated with APO-B level(P_adj=0.020).And rs4796793 associated wtih VLDL,TG level(P_adj<0.050).6.Association between JAK2 and STAT3 gene polymorphism and blood coagulation markers of IS with phlegm and blood stasis syndrome?1?No significant association between rs1887429?rs2274472?rs4796793 and blood stasis syndrome of IS with phlegm and blood stasis syndrome(P_adj>0.050).?2?After gender-specific stratification analysis,rs2274472 was significantly associated with D-D level of?male IS with phlegm and blood stasis syndrome(P_adj=0.040);while,rs1887429 and rs4796793were not associated with male IS with phlegm and blood stasis syndrome(P_adj>0.050).Rs1887429,rs2274472 and rs4796793 were all not associated with female IS with phlegm and blood stasis syndrome(P_adj>0.050).7.Association between JAK2 and STAT3 gene polymorphism and blood coagulation markers of CHD with phlegm and blood stasis syndrome?1?rs1887429 was significantly associated with PLT level of CHD with phlegm and blood stasis syndrome(P_adj<0.050),and rs4796793with APTT,PT(P_adj<0.050).?2?In the male CHD with phlegm and blood stasis syndrome group:rs2274472 was significantly associated with D-D level(P_adj=0.010);rs1887429 and rs4796793 was not associated with coagulation function index(P_adj>0.05).In the female CHD with phlegm and blood stasis syndrome group:significant associations were found between rs1887429and PTA,as well as rs2274472 and D-D(all P_adj<0.050).Conclusions:JAK2 gene variants rs1887429,rs2274472,and STAT3 gene variants rs4796793 may not increase the risk of IS with phlegm and blood stasis syndrome or IS with phlegm and blood stasis syndrome.While,JAK2 gene variants rs1887429 may affect the occurrence of female CHD with phlegm and blood stasis syndrome,rs2274472 may affect the occurrenceoffemaleISwithphlegmandbloodstasis syndrome.Rs2274472 variants of the JAK2 gene may affect the lipid metabolism of IS patients and CHD patients with phlegm and blood stasis syndrome.rs1887429 may affect lipid metabolism in patients withCHD with phlegm and blood stasis syndrome.STAT3 gene rs4796793 may affect the coagulation function of IS with phlegm and blood stasis syndrome;JAK2 gene rs1887429,rs2274472 polymorphisms,STAT3gene rs4796793 may affect coagulation function in patients with CHD syndrome.