Association Study Of TRAP1 Genetic Variants With Susceptibility And Glucocorticoids Efficacy Of Systemic Lupus Erythematosus

Part 1 Association Study of TRAP1 Gene Polymorphisms with Susceptibility and Glucocorticoids Efficacy of Systemic Lupus ErythematosusObjective This study explored if TRAP1 gene polymorphisms in patients with systemic lupus erythematosus(SLE)are associated with disease susceptibility and the efficacy of glucocorticoids(GCs).Methods A case control study enrolled 479 SLE patients and 479 healthy controls was performed to explore the association between TRAP1 gene polymorphisms and susceptibility to SLE,then 433 SLE patients included in the case control study were followed to investigate the relationship between TRAP1 gene polymorphisms and efficacy of GCs.We also compared the improvement in health related quality of life(HRQOL)of patients among different genotypes of TRAP1 gene.The Benjamini-Hochberg(BH)method was used to correct for multiple comparison.Results In case control study,the significant association between rs8055172 and the susceptibility to SLE was discovered in the dominant model(OR=2.268,95 %CI=1.710-3.009,P=1.36×10-8;PBH=3.54×10-7),which is further supported by the different distributions of haplotype TT and TC of rs2072379 and rs8055172(OR=2.124,95 % CI=1.654-2.729,PBH=6.93×10-9;OR=0.692,95 % CI=0.567-0.844,PBH=4.26×10-4).In the dominant model,rs3751842 and rs1639150 may be associated with fever of SLE patients(OR=1.794,95%CI=1.197-2.689,PBH=0.035;OR=0.579,95 % CI=0.400-0.838,PBH=0.028),while rs2072379 and rs12597773 related to oral ulcers(OR=2.161,95 % CI=1.300-3.592,PBH=0.021)and hematological system(OR=1.713,95 % CI=1.176-2.495,PBH =0.035)respectively.In the follow-up study,rs6500552 showed a significant relationship with the efficacy of GCs in SLE patients in the dominant model(OR=0.416,95 % CI=0.271-0.639.PBH=0.004).Besides,rs3794701 was associated with the improvement in role-emotional(RE)of SLE patients in dominant model(0(0-0)vs.0(0-33.33),PBH=0.029).Conclusion The results supported that TRAP1 gene polymorphisms may be associated with susceptibility to SLE and efficacy of GCs in SLE patients.Part 2 Association Study of TRAP1 Gene CNV with Susceptibility and Clinical Characteristics of Systemic Lupus ErythematosusObjective To explore whether TRAP1 gene copy number variation(CNV)have an association with susceptibility and clinical characteristics of systemic lupus erythematosus(SLE).Methods A study enrolled 304 SLE patients and 391 healthy controls was used to investigate the association between TRAP1 gene CNV and SLE susceptibility.Then,304 SLE patients were divided into copy number=2 group and copy number>2 group to investigate the association between TRAP1 gene CNV and disease activity or clinical characteristics of SLE.Accu Copy TM Kit was used to detect the TRAP1 gene copy number.Data analyses were performed by SPSS 10.01 software,the suitable method is selected among t test,rank sum test and ?2 test for analysis based on the data type and distribution,univariate and multivariate logistic regression analysis were performed to investigate the association between TRAP1 gene CNV and susceptibility and clinical characteristics of SLE.Results The CNV of TRAP1 gene showed an association with the susceptibility to SLE(crude OR=5.257,95%CI=1.108-24.937,P=0.037;Adjusted OR=5.578,95%CI=1.172-26.556,P=0.031).There was no association between TRAP1 gene CNV and score of SLE disease activity index(SLEDAI)(Z=-0.117,P=0.907).The CNV of TRAP1 gene had a marginal association with skin lesions in SLE(OR=0.130,95%CI=0.016-1.069,P=0.058),but it disappeared after adjusting for potential confounders(OR=0.288,95%CI=0.029-2.831,P=0.286,PBH=0.808).There was no correlation between TRAP1 gene CNV and arthritis,alopecia,oral ulcers,fever,hematologic disorder,lupus nephritis as well as photosensitivity in SLE(P>0.05).Conclusion The CNV of TRAP1 gene may be associated with susceptibility to SLE.Increased TRAP1 gene copy number may be a risk factor for SLE.