Analysis of Neuropeptide S Receptor Gene (NPSR1) Polymorphism in Rheumatoid Arthritis 英文参考文献.docVIP
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Analysis of Neuropeptide S Receptor Gene (NPSR1) Polymorphism in Rheumatoid Arthritis 英文参考文献
AnalysisofNeuropeptideSReceptorGene(NPSR1)
PolymorphisminRheumatoidArthritis
MauroD’Amato1,MarcoZucchelli1,MariaSeddighzadeh2,FrancescaAnedda1,3,StaffanLindblad2 ,Juha
Kere1,LarsAlfredsson4,LarsKlareskog2,LeonidPadyukov2*
1DepartmentofBiosciencesandNutrition,KarolinskaInstitutet,Stockholm,Sweden,2DepartmentofMedicine,KarolinskaInstitutet,Stockholm,Sweden,3Instituteof
NeurogeneticsandNeuropharmacology,CNR,Monserrato,Italy,4InstituteofEnvironmentalMedicine,KarolinskaInstitutet,Stockholm,Sweden
Abstract
Background:PolymorphismintheneuropeptideSreceptorgeneNPSR1isassociatedwithasthmaandinflammatorybowel
disease.NPSR1isexpressedinthebrain,whereitmodulatesanxietyandresponsestostress,butalsoinothertissuesand
celltypes including lymphocytes,thelungs,andtheintestine, whereitappearstobe up-regulated ininflammation.We
soughttodeterminewhethergeneticvariabilityattheNPSR1locusinfluencesthesusceptibilityandclinicalmanifestationof
rheumatoidarthritis(RA).
Methodology/PrincipalFindings:FromtheEpidemiologicalInvestigationofRheumatoidArthritis(EIRA)case-controlstudy,
1,888 rheumatoid arthritis patients and 888 controls were genotyped for 19 single-nucleotide polymorphisms (SNPs)
spanning the entire NPSR1 gene and 220KB of DNA on chromosome 7p14. The association between individual genetic
markersandtheirhaplotypiccombinations,respectively,anddiagnosisofRA,presenceofautoantibodiestocitrullinated
proteins (ACPA), and disease activity score based on 28 joints (DAS28) was tested. There was no association between
diagnosis of RA and NPSR1 variants. However, several associations of nominal significance were detected concerning
susceptibilitytoACPA-negativeRAanddiseaseactivitymeasures(DAS28).Amongthese,theassociationofSNPrs324987
withACPA-negativeRA[(p=0.004,OR=0.674(95%CI0.512–0.888)]andthatofSNPrithDAS28[p=0.0002,
OR=0.380(95%CI0.227–0.635)]remainedsignificantaftercorrectionformultiplecomparisons.
Conclusions/Significance:NPSR1polymorphismmayberelevanttoRAsusceptibilityandits
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