Association between the Interleukin-6 Promoter Polymorphism ？174GC and Serum Lipoprotein(a) Concentrations in Humans 英文参考文献.docVIP

AssociationbetweentheInterleukin-6Promoter Polymorphism2174G/CandSerumLipoprotein(a) ConcentrationsinHumans HeinerK.Berthold1,2*,MatthiasLaudes3,4,WilhelmKrone3,IoannaGouni-Berthold3 1Research Group on Geriatrics, Evangelical Geriatrics Center Berlin (EGZB), Charite′ University Medicine Berlin, Berlin, Germany, 2Lipid Clinic at the Interdisciplinary MetabolismCenter,CampusVirchowClinic,Charite′ UniversityMedicineBerlin,Berlin,Germany,3CenterofEndocrinology,Diabetes,andPreventiveMedicine,University ofCologne,Cologne,Germany,4DepartmentofInternalMedicineIandClusterofExcellenceinInflammationatInterfaces,UniversityofKiel,Kiel,Germany Abstract Background:Lipoprotein(a)[Lp(a)]isanindependentriskfactorforcardiovasculardisease.Theinterleukin-6(IL-6)receptor antagonist tocilizumab has been shown to lower serum Lp(a) concentrations. We investigated whether the IL-6 single nucleotidepolymorphism2174G/CisassociatedwithbaselineserumLp(a)concentrations. Methodology/PrincipalFindings:Wedivided2321subjectsfromtheLipidAnalyticCologne(LIANCO)cohortinto2groups, theoneswithsubstantiallyelevatedLp(a),definedasconcentrations$60mg/dl(n=510),andtheoneswithLp(a),60mg/ dl(n=1811).TheassociationwiththegenotypesGG(33.7%),GC(50.75%)andCC(15.55%)wasinvestigated.TheGCand the CC genotype were associated with a significantly increased odds ratio of having substantially elevated Lp(a) concentrations (OR=1.3, 95% CI 1.04 to 1.63, P=0.02 and OR=1.44, 95% CI 1.06 to 1.93, P=0.018). These associations remainedsignificantafteradjustingforage,sex,smokingbehavior,bodymassindex,serumlipoproteins,hypertensionand diabetes. Of these covariates, only LDL cholesterol was significantly and independently associated with elevated Lp(a) concentrations. Conclusions/Significance:TheIL-6singlenucleotidepolymorphism2174G/Cisassociatedwithincreasedoddsofhaving elevatedLp(a).WhetherthisassociationplaysaroleintheLp(a)-loweringeffectsofIL-6receptorantagonistsremainstobe established. Citation: Berthold HK, Laudes M, Kron