Angiogenin Levels and ANG Genotypes Dysregulation in Amyotrophic Lateral Sclerosis 英文参考文献.docVIP

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Angiogenin Levels and ANG Genotypes Dysregulation in Amyotrophic Lateral Sclerosis 英文参考文献.doc

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Angiogenin Levels and ANG Genotypes Dysregulation in Amyotrophic Lateral Sclerosis 英文参考文献

AngiogeninLevelsandANGGenotypes:Dysregulationin AmyotrophicLateralSclerosis RussellLewisMcLaughlin1,2*,JuliePhukan2,3,WilliamMcCormack4,DavidS.Lynch2,5 ,Matthew Greenway5,SimonCronin2,5,JeanSaunders6,AgnieskaSlowik7,BarbaraTomik7,PeterM.Andersen8, DanielG.Bradley1,PhilJakeman4,OrlaHardiman2,3 1Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland, 2Department of Neurology, Beaumont Hospital, Dublin, Ireland, 3Trinity College Institute of Neuroscience,TrinityCollegeDublin,Dublin,Ireland,4HumanScienceResearchUnit,FacultyofEducationandHealthSciences,UniversityofLimerick,Limerick,Ireland, 5Royal College of Surgeons Ireland, Dublin, Ireland, 6Statistical Consulting Unit, University of Limerick, Limerick, Ireland, 7Department of Neurology, Jagiellonian University,Krakow,Poland,8DepartmentofPharmacologyandClinicalNeurosciences,Umea? UniversityHospital,Umea?, Sweden Abstract Objective:Todeterminewhether5singlenucleotidepolymorphisms(SNPs)associatewithALSin3differentpopulations. WealsoassessedthecontributionofgenotypetoangiogeninlevelsinplasmaandCSF. Methods:AllelicassociationstatisticswerecalculatedforpolymorphismsintheANGgenein859patientsand1047controls from Sweden, Ireland and Poland. Plasma, serum and CSF angiogenin levels were quantified and stratified according to genotypes across the ANG gene. The contribution of SNP genotypes to variance in circulating angiogenin levels was estimatedinpatientsandcontrols. Results:AllSNPsshowedassociationwithALSintheIrishgroup.TheSNPreplicatedintheSwedishcohort.No SNPassociatedinthePolishcohort.Age-andsex-correctedcirculatingangiogeninlevelsweresignificantlylowerinpatients than in controls (p,0.001). An allele dose-dependent regulation of angiogenin levels was observed in controls. This regulationwasattenuatedintheALScohort.AsignificantpositivecorrelationbetweenCSFplasmaangiogeninlevelswas presentincontrolsandabolishedinALS. Conclusions:ANGvariantsassociatewithALSintheIrishandSwedishpopulations,butno