Polymorphisms in the Inflammatory Genes CIITA, CLEC16A and IFNG Influence BMD, Bone Loss and Fracture in Elderly Women 英文参考文献.docVIP
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Polymorphisms in the Inflammatory Genes CIITA, CLEC16A and IFNG Influence BMD, Bone Loss and Fracture in Elderly Women 英文参考文献
PolymorphismsintheInflammatoryGenesCIITA,
CLEC16AandIFNGInfluenceBMD,BoneLossand
FractureinElderlyWomen
MariaSwanberg1,2,FionaE.McGuigan1,KaisaK.Ivaska3,PaulGerdhem4,5,KristinaAkesson? 1,6*
1ClinicalandMolecularOsteoporosisResearchUnit,DepartmentofClinicalSciences,LundUniversity,Sweden, 2NeurodegenerationandInflammationGeneticsUnit,
DepartmentofExperimentalMedicalScience,LundUniversity,Sweden,3DepartmentofCellBiologyandAnatomy,InstituteofBiomedicine,UniversityofTurku,Turku,
Finland, 4Department ofClinical Science,Interventionand Technology,KarolinskaInstitute, Stockholm,Sweden, 5Department ofOrthopaedics, Karolinska University
Hospital,Stockholm,Sweden,6DepartmentofOrthopaedics,Ska?ne UniversityHospital,Malmo¨,Sweden
Abstract
Osteoclastactivityandthefinebalancebetweenboneformationandresorptionisaffectedbyinflammatoryfactorssuchas
cytokinesandTlymphocyteactivity,mediatedbymajorhistocompatibilitycomplex(MHC)molecules,inturnregulatedby
the MHC class II transactivator (MHC2TA). We investigated the effect of functional polymorphisms in the MHC2TA gene
(CIITA),andtwoadditionalgenes;C-typelectindomain16A(CLEC16A),inlinkagedisequilibriumwithCIITAandInterferon-c
(IFNG),aninducerofCIITA;on bonedensity, boneresorption markers,bonelossandfracture riskin 75year-oldwomen
followedforupto10years(OPRAn=1003)andinyoungadultwomen(PEAK-25n=999).CIITAwasassociatedwithBMDat
age 75 (lumbar spine p=0.011; femoral neck (FN) p=0.049) and age 80 (total body p=0.015; total hip p=0.042; FN
p=0.028). Carriers of the CIITA rs3087456(G) allele had 1.8–3.4% higher BMD and displayed increased rate of bone loss
between age 75 and 80 (FN p=0.013; total hip p=0.030; total body p=3.8E25). Despite increasing bone loss, the
rs3087456(G) allele was protective against incident fracture overall (p=0.002), osteoporotic fracture and hip fracture.
CarriersofCLEC16AandIFNGvariantalleleshadlowerBMD(p,0.05)andultrasoundparametersandalowerriskofincident
fracture(CLEC16A,p=0.011).In
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