Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis 英文参考文献.docVIP

Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis 英文参考文献.doc

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Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis 英文参考文献

SexDifferentialGeneticEffectofChromosome9p21on SubclinicalAtherosclerosis Hsiu-FenLin1,2,Pei-ChienTsai3,Ruey-TayLin1,2,Gim-TheanKhor1,Sheng-HsiungSheu4,5 ,Suh-Hang HankJuo3,6 * 1DepartmentofNeurology,KaohsiungMedicalUniversityHospital,Kaohsiung,TaiwanAuthority,2DepartmentofNeurology,CollegeofMedicine,KaohsiungMedical University,Kaohsiung,TaiwanAuthority,3DepartmentofMedicalResearch,KaohsiungMedicalUniversityHospital,Kaohsiung,TaiwanAuthority,4DivisionofCardiology, DepartmentofInternalMedicine,KaohsiungMedicalUniversityHospital,Kaohsiung,TaiwanAuthority,5DepartmentofInternalMedicine,CollegeofMedicine,Kaohsiung MedicalUniversity,Kaohsiung,TaiwanAuthority,6DepartmentofMedicalGenetics,CollegeofMedicine,KaohsiungMedicalUniversity,Kaohsiung,TaiwanAuthority Abstract Background:Chromosome9p21hasrecentlybeenshowntobeariskregionforabroadrangeofvasculardiseases.Since carotidintima-mediathickness(IMT)andplaqueareindependentpredictorsforvasculardiseases,theassociationbetween 9p21andthesetwophenotypeswasinvestigated. Methodology/PrincipalFindings:Carotidsegment-specificIMTandplaqueswereobtainedin1083stroke-andmyocardial infarction-free volunteers. We tested the genotypes and haplotypes of key single nucleotide polymorphisms (SNPs) on chromosome9p21fortheassociationswithcarotidIMTandplaque.Multivariatepermutationanalysesdemonstratedthat carriers of the T allele of SNP rs1333040 were significantly associated with thicker common carotid artery (CCA) IMT (p=0.021)andinternalcarotidartery(ICA)IMT(p=0.033).TheriskGalleleofSNPrs2383207wasassociatedwithICAIMT (p=0.007).CarriersoftheCalleleofSNPrs1333049werefoundtobesignificantlyassociatedwiththickerICAIMT(p=0.010) and the greater risk for the presence of carotid plaque (OR=1.57 for heterozygous carriers; OR=1.75 for homozygous carriers). Haplotype analysis showedaglobalpvalueof 0.031 forICAIMT and0.115 forthepresence ofcarotid plaque. Comparingwiththeotherhaplotypes,theriskTGChaplotypeyieldedanadjustedpvalueof0.011and0.017forthicker

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