Association Analysis Between The Susceptibility Gene CD80and Clinical Features Of Systemic Lupus Erythematosus In Chinese Han Population

Background Systemic lupus erythematosus (SLE) is a chronic,relapsing-remitting autoimmune disorder that involves multiple organ systems. Itsprevalence, incidence, and disease severity are known to vary among ethnic groups.The reasons for the ethnic disparities in the prevalence of systemic lupus erythematosus(SLE) and the relative high frequency of SLE risk alleles in the population are not fullyunderstood. We have found more than one susceptibility genes associated with SLEas of early2014, located on2p13(TET3),3q13.3(CD80),4q25(LEF1),6p21.3(HLA-DQA2),7q32(TNPO3),10q21(ARID5B) and the like. SLE genotype-phenotype analysis suggests that some genes, such as CD40was associated withnephritis and arthritis, TRAF3IP2was associated with pericarditis. In2013, we haveidentified five novel susceptibility genes for SLE in a Meta-analysis of Chinese HanPopulation, including CD80(P=2.5E-16). Expanded sample size was used to clarify thecorrelation with phenotype of SLE.Objective1) Analysis the association between CD80(rs6804441) and SLE.2)Investigated the CD80relationships with disease subphenotypes, including renalnephritis, photosensitivity, ANA, dsDNA,SM,RNP,C3,age at diagnosis, malar rash,discoid rash, immunological disorder, oral ulcer, hematological disorder, neurologicaldisorder,serositis, arithritis and vasculitis. Methods1)2208patients and2208controls were genotyped by Sequenom MassArraysystem.2)Previous analysis of Meta Data were combined(Note:a total number of4348unrelated cases and6679unrelated controls were involved in this study).3)PLINK1.07was used for statistical analysis of the association between CD80(rs6804441) and SLE.4) PLINK1.07was used for statistical analysis of genetic model.5) PLINK1.07was used for statistical analysis of positive phenotype-negativephenotype and subphenotype-controls.Results1)2208case-2208control: CD80(rs6804441) was associated with SLE(P=1.02E-3);4348case-6679control: CD80(rs6804441) was significant associated withSLE(P=8.89E-19).2)positive phenotype-negative phenotype: CD80(rs6804441) has no evidence withSLE phenotype. Age <20years (P=0.17), butterfly erythema (P=0.88), discoid rash (P=0.86), light sensitivity (P=0.75), vasculitis (P=0.68), kidney disease (P=0.28),hematologic abnormalities (P=0.42), neurological abnormalities (P=0.71), serositis (P=0.17), oral ulcers (P=0.83), arthritis (P=0.75), ANA (P=0.73), dsDNA (P=0.76),SM (P=0.92), RNP (P=0.32), C3(P=0.83), immunological abnormalities (P=0.99).3)subphenotype-control: CD80(rs6804441) allele frequencies between serositisnegative patients and controls has statistical significance (OR=0.67,95%CI:0.61-0.73,P=5.43E-19), serositis-positive patients wan not associated with controls (OR=0.81,95%CI:0.62-1.08, P=0.147), the remaining16kinds of subphenotype wereassociated with controls. Conclusions Our study suggested CD80(rs6804441) was significantly associatedwith SLE (P=8.89E-19). The association of CD80(rs6804441) genotype and17kindsphenotype of SLE was not yet found.