biostudies-literatureZhao JBLRD VANCATS NIH HHSNCRR NIH HHSNIDDK NIH HHSNIAID NIH HHSNCI NIH HHSNIAMS NIH HHSWellcome TrustNIGMS NIH HHSPHS HHS242-52https://www.ebi.ac.uk/biostudies/studies/S-EPMC4717392biostudies-literatureUnknown75(1)<h4>Objectives</h4>Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association.<h4>Methods</h4>Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR.<h4>Results</h4>The strongest association signal was detected at rs1876453 in intrAnnals of the rheumatic diseasesPreferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA.PMC4717392RC1 AR058621R01AR057172UL1 TR000154UL1 TR000430I01 BX001834P60AR062755P60 AR062755R21AI070304R01 CA141700R01AI063274K24 AI078004LRPAI071651UL1 RR024999U54RR023417P30 AR053483K08AI083790R01AR051545U01AI101934T32AR07534R01 AI070983UL1 RR029882R21 AI070304R01AR042460P60 AR030692P30 DK57516UL1 TR000004UL1RR025741R01 AR064820R01AR043274UL1 TR001417T32 AR007534R01 AR042460R01 AR043274UL1 RR025777U19AI082714P01AR049084UL1 RR025014U01 AI101934R01AI070983RC1AR058621U54 GM104938UL1 TR000371P30AR048311UL1 TR001422P01AI083194R01 AR043814P30GM103510UL1RR025777P60AR053308U19 AI082714UL1 TR001425N01 AR062277UL1RR025014UL1 TR002319R01AR43727P30 AR048311P20RR020143UL1RR024999UL1 RR025741R37 AI024717P60 AR053308R37AI024717K24AI078004R01 AR057172R01 AR033062R01 AI063274R01 AR043727UL1TR000004P30 GM103510UL1RR029882K24AR002138K08 AI083790R01CA141700P30 CA046934P01 AI083194R01 AR051545P30 DK057516P20 RR020143K24 AR002138R01AR043814P30AR053483P01 AR049084R01AR033062P30AR055385UL1 TR001082Yette GAGlenn SBTaylor RLReveille JDWu HKaufman KMUlgiati DTsao BPComeau MEAlarcon GSLough KMCriswell LAJames JARamsey-Goldman RFreedman BIMerrill JTLangefeld CDAdler AJVila LMKim DBIOLUPUS and GENLES NetworksScofield RHWilliams AHZiegler JTGuthridge JMMarion MNiewold TBKimberly RPAlarcon-Riquelme MEGaffney PMNg HLAnaya JMLee HSGilkeson GSVyse TJBrown EEHarley JBEdberg JCZhao JAbraham LJJacob COGiles BMPetri MASivils KMBae SCStevens AMBoackle SAKelly JAKamen DLfalsePreferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA.<h4>Objectives</h4>Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association.<h4>Methods</h4>Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR.<h4>Results</h4>The strongest association signal was detected at rs1876453 in intr2016-01-01T00:00:00Z2016 Jan2026-05-05T19:20:22.437Z2019-03-27T02:07:06ZS-EPMC47173922518029310.1136/annrheumdis-2014-205584