Association Study Of BLK Gene Polymorphisms And Clinical Characteristic In Patients With Systemic Lupus Erythematosus

ObjectivePrevious studies are inconclusive on the relationships between BLK gene polymorphisms and clinical features of systemic lupus erythematosus?SLE?.We thus speculated that previous inconsistent findings might be attributable to unadjusted and residual confounding by disease duration,misclassification bias of outcomes or population heterogeneity.The present study aimed to give some evidence on BLK effects in shaping the SLE phenotypes in a Han population of central China using two independent patient cohorts with adjusting for potential confounding factors and using new cases data for reducing potential bias.MethodsPatients with SLE were recruited from two different sources according with American College of Rheumatology?ACR?criteria.After obtaining the informed consent,genomic DNA samples were extracted from peripheral blood of all patients.Clinical phenotypes and covariates of the patients were obtained,including the ACR classification criteria,laboratory parameters,gender,age at disease onset,disease duration and the recruiting centers.All these SNPs were genotyped using SNPscan technology.Associations between BLK single nucleotide polymorphisms?SNPs?and susceptibility to SLE in this study were estimated using data of 1205 health controls previously reported in same population.Genotypes for 3 targeted SNPs of BLK were compared between cases positive and negative for each of the ACR classification criteria and laboratory parameters.Potential confounding factors were adjusted.In addition,the genotyping data of the control group were used for conditional analysis to explore whether the association between BLK gene and SLE was caused by kidney damage.The expression quantitative trait locus?e QTL?data were also extracted from the public databases?GTEx database and NCDB database?for the selected SNPs.Drugbank database was used to obtain information on drug target genes for the treatment of lupus nephritis and STRING database was used to analyze the interaction between the proteins encoded by BLK gene and the drug target genes for lupus nephritis.ResultsThe data showed that rs2618479 and rs7812879 were associated with renal disorder[OR=1.51?95%CI:1.15,1.99?and 1.61?95%CI:1.21,2.14?,P_corr=0.033 and 0.011,respectively]and proteinuria[OR=1.47?95%CI:1.12,1.95?and 1.52?95%CI:1.14,2.03?,P_corr=0.040 and 0.048,respectively].The consistent associations were observed in two independent centers as well as new cases group.The result of meta-analysis for the rs2618479 was also significant[OR=1.35?95%CI:1.12,1.62?].Furthermore,although all associations have no statistical significance,in view of the relatively bigger effect sizes in patients with renal disorder,we suspected that the association of BLK with SLE may be partially caused by the association with renal disorder.In addition,the results of e QTL analysis demonstrated that the rs2618479 and rs7812879 were significantly associated with the expression of BLK in whole blood and several immune cells:the rs2618479(P and 2.71×10^-8in B cell).In the analysis of the interaction,there was an interaction between proteins encoded by BLK gene and STAT3 gene.ConclusionIn conclusion,we demonstrated associations between BLK SNPs and SLE specific manifestations in a Chinses Han population.In the case-only study,rs2618479 and rs7812879 showed more prominent effect for renal disorder and proteinuria than for other clinical features.In the analysis of drug target information,BLK gene may be a potential drug target for treating lupus nephritis.Further lager independent studies in distinct ethnical populations are required to define the precise role of this genes for SLE clinical features.