Association Study Of FKBP4 And FKBP5 Gene Polymorphisms With Susceptibility And Glucocorticoid Efficacy Of Systemic Lupus Erythematosus

Object To explore the associations of FKBP4 and FKBP5 gene polymorphisms with disease susceptibility and glucocorticoid（GC）efficacy of systemic lupus erythematosus（SLE）.The anxiety,depression,health-related quality of life（HRQOL）of SLE patients were evaluated to explore the associations of FKBP4 and FKBP5gene polymorphisms with the occurrence and improvement of anxiety,depression,as well as the baseline score and improvement of HRQOL.Methods In the case-control study,subjects were collected from the First Affiliated Hospital and the Second Affiliated Hospital of Anhui Medical University in Hefei,Anhui Province.A total of 541 SLE patients and 543 healthy controls were collected to explore the associations of FKBP4 and FKBP5 gene polymorphisms with SLE susceptibility.14-item Hamilton Anxiety Rating Scale（HAMA）and 24-item Hamilton Depression Rating Scale（HAMD）were used to assess anxiety and depression of SLE patients,respectively.Short-Form-36 Health Survey（SF-36）was used to assess health-related quality of life（HRQOL）of SLE patients.These scores were used to explore the associations of FKBP4 and FKBP5 gene polymorphisms with anxiety,depression and HRQOL in SLE patients.In the follow-up study,485SLE patients who met the inclusion and exclusion criteria were followed up for 12weeks.Finally,466 SLE patients completed the follow-up.Then,SLE patients were divided into GCs-sensitive group and GCs-insensitive group to explore the associations of FKBP4 and FKBP5 gene polymorphisms with GC efficacy.During the follow-up,HAMA,HAMD and HRQOL scores of SLE patients were recorded,and the difference of each score between the score at the end of follow-up（12-week）and the baseline（0-week）was compared to explore whether there was an association between FKBP4 and FKBP5 gene polymorphisms and the improvement of anxiety,depression and HRQOL in SLE patients.Chi-square test,t test,univariate and multivariate logistic regression analyses were performed to analyzed the data.Results In the case-control study,in the dominant model,rs4713904(OR=1.947,95%CI=1.163-3.261,P=0.011,adjusted OR=2.071,95%CI=1.222-3.509,P=0.007;P_BH=0.037),rs9368878(OR=2.564,95%CI=1.570-4.189,P=1.7×10^-4,adjusted OR=2.765,95%CI=1.673-4.569,P=7.9×10^-5;P_BH=0.001)and rs7757037(OR=2.358,95%CI=1.454-3.825,P=5.1×10^-4,adjusted OR=2.428,95%CI=1.483-3.973,P=4.2×10^-4;P_BH=0.003)of FKBP5 were associated with depression in SLE patients.In the follow-up study,rs4713904 of FKBP5 was associated with GC efficacy in male with SLE(OR=0.179,95%CI=0.060-0.536,P=0.001,P_BH=0.011).The C minor allele may be related to the decreased insensitivity to GCs in SLE patients.In the dominant model,rs755658 of FKBP5 was associated with the improvement in social function（SF）(0（0-12.50）vs 12.50（0-25.00）,P=0.002,P_BH=0.022)and mental component summary（MCS）(2.25（-2.00-10.58）vs 5.63（0-22.63）,P=0.005,P_BH=0.028).rs4713907 was associated with improvement in total score of HRQOL(5.47（0.06-14.58）vs 2.00（3.13-9.31）,P=0.004,P_BH=0.018),bodily pain（BP）(10.00（0-24.50）vs 0（-10.00-22.00）,P=0.005,P_BH=0.018),and MCS(3.13（-1.00-12.00）vs0（-3.63-5.63）,P=0.004,P_BH=0.018).In recessive model,rs12582595 of FKBP4 was associated with general health（GH）improvement(0（-5.00-10.00）vs-5.00（-15.00-0）,P=0.003,P_BH=0.033).However,in our present study,no association was found between FKBP4 and FKBP5 gene polymorphisms and the susceptibility and anxiety of SLE patients.Conclusion FKBP5 gene polymorphism may be associated with depression,GC efficacy,and the improvement of HRQOL in SLE patients.The genetic polymorphism of FKBP4 may be associated with the improvement of HRQOL in SLE patients.