Association Of GWAS-supported Variants With Risk Of Ischemic Stroke And Its Patients With Wind-phlegm Blocking Collaterals Symptom And Qi-deficiency Blood-stasis Symptom

Aim: Recent genome-wide association studies(GWAS)have identified that rs2107595,rs2200733 and rs6843082 polymorphisms are significantly associated with ischemic stroke(IS)in Europeans.The current study aims to examine the association of GWAS-supported rs2107595,rs2200733 and rs6843082 polymorphisms with risk of IS and IS patients with wind-phlegm blocking collaterals symptom and Qi-deficiency blood-stasis symptom,as well as their serum lipid level in Chinese Han population from Guangxi.Methods:The case-control study including 816 IS patients(465 males and 351 females)and 816 controls(433 males and 383 females)were investigated in the Chinese Han population from Guangxi area.Rs2107595,rs2200733 and rs6843082 polymorphisms were genotyped using the Sequenom Mass Array i PLEX.Total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterin(LDL-C)were measured using the HITACHI 7600 biochemical autoanalyzer.Statistical analysis were performed using SPSS 16.0 for windows(SPSS Inc.,Chicago,IL,USA)and PLINK software(http://pngu.mgh.harvard.edu/~purcell/plink/).Results:(1)Hardy-Weinberg Equilibrium(HWE)test: the genotype distribution in controls of rs2107595,rs2200733 and rs6843082 polymorphisms were in line with HWE(all P>0.050).(2)Genetic association of GWAS-supported variants with IS in Guangxi Han Chinese: there were no statistical associations between rs2107595,rs2200733 and rs6843082 polymorphisms and IS in all genetic models(each genetic model: all P>0.050,Padj >0.050).(3)Association of GWAS-supported variants with IS patients with wind-phlegm blocking collaterals symptom and Qi-deficiency blood-stasis symptom: variants rs2107595,rs2200733 and rs6843082 showed no significant association with IS patients with wind-phlegm blocking collaterals symptom or Qi-deficiency blood-stasis symptom(each genetic model: all P>0.050,Padj >0.050).But,the rs6843082 polymorphism presented a significant association with male IS patients with Qi-deficiency blood-stasis symptom(additive model: Padj=0.049;dominant model: Padj= 0.025).(4)Genetic association of GWAS-supported variants with the lipid level of IS patients:(1)In total samples,the rs6843082 polymorphism was significantly associated with serum TC in IS individuals(additive model:Padj=0.017;dominant model: Padj= 0.023),while no statistical differences were detected between rs2107595,rs2200733 polymorphisms and the serum TC?TG?HDL-C?LDL-C in IS patients(each genetic model: all Padj >0.050).(2)In males,the rs2107595 polymorphism showed a significant association with serum TG(additive model: Padj=0.008;dominant model: Padj= 0.003),and the rs2200733 polymorphism was associted with serum LDL-C in male IS patients(dominant model: Padj= 0.044).(3)In females,the rs2107595,rs2200733 and rs6843082 polymorphisms were significantly associated with serum TC in female IS individuals(Padj <0.050).(5)Association of GWAS-supported variants with the lipid level of IS patients with wind-phlegm blocking collaterals symptom and Qi-deficiency blood-stasis symptom:(1)In total samples,the rs2107595 polymorphism was significantly associated with serum TC level in patients with wind-phlegm blocking collaterals symptom and Qi-deficiency blood-stasis symptom(Padj<0.050).Besides,the rs6843082 polymorphism was significantlyassociated with serum TC,HDL-C levels in patients with Qi-deficiency blood-stasis symptom(Padj<0.050).(2)In males,the rs2107595 polymorphism showed significant associations with serum TG in male patients with wind-phlegm blocking collaterals symptom and Qi-deficiency blood-stasis symptom(Padj<0.050),and it also significantly associated with serum TC in male patients with wind-phlegm blocking collaterals symptom(Padj<0.050).Additionally,the rs2200733 variant showed significant associations with serum TC,TG,HDL-C levels in male patients with wind-phlegm blocking collaterals symptom(Padj<0.050).The rs6843082 polymorphism also showed significant associations with serum TC,HDL-C levels in male patients with Qi-deficiency blood-stasis symptom(Padj<0.050).(3)In females,the rs2107595 polymorphism was significantly associated with serum TC,LDL-C levels in female patients with wind-phlegm blocking collaterals symptom(Padj<0.050).Besides,the rs2107595 and rs2200733 polymorphisms were significantly associated with serum TC level in female patients with Qi-deficiency blood-stasis symptom(Padj<0.050).Conclusions: GWAS-identified rs2107595,rs2200733 and rs6843082 polymorphisms may be not associated with the susceptibility of IS in Chinese Han population from Guangxi area,but the rs6843082 polymorphism may influence the occurrence of male IS patients with Qi-deficiency blood-stasis symptom;Meanwhile,rs2107595,rs2200733 and rs6843082 polymorphisms may influence the lipid metabolism of IS as well as its patients with wind-phlegm blocking collaterals symptom and Qi-deficiency blood-stasis symptom.