Association Of IL-1β Polymorphisms And Plasma Levels With Chronic Heart Failure

Part I Association of IL-1β plasma levels with chronic heart failure:A case-control study in Chinese patientsBackgroundHeart failure has been major health concern affecting 1-2%of world adult population.Role of various cytokines in chronic heart failure(CHF)have been demonstrated in different populations,however association of an important cytokines,interleukin 1β is ill documented.In the present study,we explored the association of plasma levels of IL 1b in healthy controls and different clinical categories of CHF with susceptibility to development of heart failure.Materials and MethodsThree hundred fifty-four CHF patients admitted to Department of Cardiology at the first affiliated hospital of Soochow University were enrolled in the present study.These patients were further clinically sub categorized in to NYHA-I to Ⅳ based on New York Heart Association criteria.Seventy-seven healthy controls were included in the current investigation.Plasma levels of IL1b was quantified by ELISA.Results(1)General characteristics analysis showed that differences by systolic blood pressure(P<0.0001),diastolic blood pressure(P<0.0001),heart rate(P<0.0001),creatinine(P=0.02)and ejection fraction(P<0.0001)were significantly between groups,while no differences were found by age,sex,total cholesterol,triglyceride,high density lipoprotein,low density lipoprotein and usea nitrogen(P>0.05).(2)CHF patients displayed higher plasma IL1b compared to healthy controls(85.51±112.3pg/ml vs.11.9±8.7pg/ml,P<0.0001).(3)Interestingly,plasma levels of IL1b was associated with severity of heart failure patients:NYHA-Ⅳ had highest levels and least quantity was noticed in NYHA-Ⅰ cases.Importantly,these observations remained valid for NYHA-Ⅲ and Ⅳ sub-groups in comparison to controls(11.9±8.7pg/ml vs.13.7±13.5 pg/ml vs.16.3±14.9 pg/ml vs.116.5±80.3 pg/ml vs.217.9±135.4pg/ml,P<0.05),Spearman rank correlation analysis indicated that the plasma levels of IL-1βwere positively related by severity of cardiac function(r=0.711,P<0.0001).ConclusionsPlasma IL1βwas associated with severity of chronic heart failure in Chinese.PartⅡ Association of IL-1β polymorphisms with chronic heart failure:A case-control study in Chinese patientsBackgroundPolymorphism in promoter region of interleukin 1β was shown to linked with cytokines levels.In the present study,we explored the association of common IL1b promoter variants with susceptibility to development of heart failure.Materials and MethodsThree hundred fifty-four CHF patients admitted to Department of Cardiology at the first affiliated hospital of Soochow University were enrolled in the present study.These patients were further clinically sub categorized in to NYHA-Ⅰ to Ⅳ based on New York Heart Association criteria.Seventy-seven healthy controls were included in the current investigation.Common promoter gene polymorphism in ILlb gene were genotyped by PCR-RFLP.Results(1)Prevalence of heterozygous and homozygous mutant for C-511T polymorphisms were significantly higher in CHF patients when compared to healthy controls(CT:P<0.0001,OR=2.91,95%CI=1.71～5.01;TT:P=0.0002,OR=5.85,95%CI=2.04～15.76).Importantly,these observations remained valid for T allele(P<0.0001,OR=2.5,95%CI=1.68～3.72).(2)The frequent of CT/TT genotype were significantly higher in NYHA-Ⅲ subgroups in comparison to controls(CT vs.CC:P<0.0001,OR=12.35,95%CI=5.18-28.46;TT vs.CC:P<0.0001,OR=28.75,95%CI=7.92-87.96),such differences were also found in NYHA-Ⅳsubgroups(CT vs.CC:P<0.0001,OR=7.09,95%CI=3.15～15.72;TT vs.CC:P<0.0001,OR=17.25,95%CI=5.19～51.51).(3)Elevated plasma levels of IL-1βwas observed in-511 mutants(CT and TT)than wild type(CC)(CC vs.CT vs.TT:32.9±30.4pg/ml vs.74.6±137.4 pg/ml vs.148.6±138.5 pg/ml,P<0.0001),indicating important function variants determining plasma levels of cytokine in both controls and patients.ConclusionsIL1b(-511)variants are predisposed to severe chronic heart failure in Chinese.