Association Of Conserved Helix-loop-helix Ubiquitous Kinase(CHUK) Gene Polymorphism With Risk Of Ischemic Stroke And Is-related Traditional Chinese Medicine Syndrome

Objective: Conserved helix-loop-helix ubiquitous kinase(CHUK)gene encode IKK? complex,which is the vital regulator of nuclear factor(NF)-kB signaling pathway,while nuclear factor f-kappa B signaling pathway is the most important inflammatory mediator in the development of Ischemic stroke(IS).Previous studies found that CHUK gene was involved in the process of lipid metabolism and regulation of diastolic blood pressure(DBP)which were risk factors of IS.This study was aimed to evaluate the association of the CHUK gene polymorphisms rs3808916,rs2230804,rs3808917 with risk of ischemic stroke(IS),its different TCM syndromes and the IS-related quantitative traits.Methods: This study included 816 ischemic stroke patients(465 males and 351 females)and 816 controls matched with sex-and age-(433males and 383 females).The SNPs genotyping were conducted by Sequenom MassArray technology.Blood pressure was measured used the mercury sphygmomanometer.Biochemical parameters of total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL)and low-density lipoprotein cholesterol(LDL)were measured by standard laboratory procedures using Hitachi 7600 Automatic BiochemistryAnalyzer.The SPSS version 16.0.software(SPSS Inc.,Chicago,IL,USA)was used to perform statistical analyses of the general data between case and control.PLINK software(http://pngu.mgh.harvard.edu/~purcell/plink/)was used to evaluate the association between CHUK gene variant rs3808916,rs2230804,rs3808917 and risk of ischemic stroke and its related phenotypes.Results: 1.Hardy-Weinberg Equilibrium(HWE)test: the genotype frequencies of the CHUK gene polymorphism rs3808916,rs2230804,rs3808917 in the control group do not deviate from HWE(all P>0.050).2.Association analysis:(1)CHUK gene polymorphism rs3808916,rs2230804,rs3808917 were not statistically significantly associated with risk of IS under the genetic models of additive,dominant,recessive and allelic(all P>0.050);(2)After gender-specific stratification analysis,CHUK gene polymorphism were not statistically significantly associated with risk of IS under the genetic models of additive,dominant,recessive and allelic(all P>0.050)? 3.Association between CHUK gene polymorphism and TCM syndrome:(1)Wind-phlegm obstruction syndrome: no significant differences were observed in the association between CHUK gene polymorphism rs3808916,rs2230804 and rs3808917 and risk of IS wind-phlegm obstruction syndrome(all P>0.050);(2)Qi-deficiency and blood-stasis syndrome: No significant differences were observed in the association between CHUK gene polymorphism rs3808916,rs2230804 and rs3808917 and risk of IS Qi-deficiency and blood-stasis syndrome(all P>0.050).4.IS-related quantitative traits analysis:(1)CHUK gene polymorphism rs2230804 was significantly associated with DBP level of IS patients(additive:P=0.035;recessive:P=0.031),rs3808917 was significantly associated with TG level of IS patients(P=0.046).CHUK gene rs3808916 polymorphism were not significantly associated with the serum levels of TC,TG,HDL ?LDL?SBP and DBP of the IS patients(all P>0.050);(2)CHUK gene polymorphism rs2230804 and rs3808917 were significantly associated with HDL level of IS patients in males(rs2230804 recessive:P= 0.022,Padj = 0.024;rs3808917 additive: P= 0.043,Padj = 0.047).rs3808916 were not significantly associated with the levels of TC,TG,HDL,LDL,SBP and DBP(all P>0.050);(3)CHUK gene polymorphism rs3808916 were significantly associated with LDL level of IS patients in females(recessive: Padj= 0.043),rs2230804 was significantly associated with TG,LDL and DBP level of IS patients in females(TG dominant: Padj = 0.030;LDL additive: P= 0.029;DBP recessive: Padj = 0.018).rs3808917 was significantly associated with TG level of IS patients in females(P= 0.011).5.Association between CHUK gene polymorphism and IS-related quantitative traits with different TCM syndrome:(1)Wind-phlegm obstruction syndrome: CHUK gene polymorphism rs3808916 was significantly associated with LDL level of IS patients(recessive: P=0.046)(2)Qi-deficiency and blood-stasis syndrome: CHUK gene polymorphism rs3808916 was significantly associated with SBP level of IS patients(additive : P = 0.043;dominant: P = 0.033);rs3808917 was significantly associated with TG level of IS patients(additive:P = 0.035;recessive: P = 0.025).Conclusions: The CHUK gene variants rs3808916,rs2230804,and rs3808917 were not associated with IS risk in the present study,but the CHUK gene variant was associated with some IS-related quantitative traits such as DBP,TG,HDL-cholesterol and LDL-cholesterol.CHUK gene polymorphism rs3808916 was associated with LDL level of IS wind-phlegm obstruction syndrome;while rs3808917 was associated with TG level of IS Qi-deficiency and blood-stasis syndrome.