Association Study Of DYNC1H1 Genetic Variants With Susceptibility And Glucocorticoids Efficacy Of Systemic Lupus Erythematosus

Objective To investigate whether DYNC1H1 gene polymorphism/copy number variation（CNV）is related to systemic lupus erythematosus（SLE）susceptibility,glucocorticoids（GCs）efficacy,anxiety,depression,and health-related quality of life（HRQOL）in SLE patients.Methods The case-control study recruited 502 SLE patients and 544 healthy controls from the First Affiliated Hospital of Anhui Medical University and the Second Affiliated Hospital of Anhui Medical University.After obtaining the consent of research subjects,blood samples were collected and questionnaire surveys were conducted.Single nucleotide polymorphisms（SNPs）and gene copy number of DYNC1H1 gene were detected by multiple SNa Pshot typing technology and Accu Copy^TM technology,respectively.In the prospective study,472 SLE patients from the case group who met the inclusion criteria were followed up for 12 weeks（453 cases completed the follow-up,19cases were lost）.Based on changes in the SLE disease activity index（SLEDAI）,we assessed the sensitivity of SLE patients to GCs treatment and completed the sensitivity groupings.The Hamilton Anxiety Rating Scale（HAMA）and Hamilton Depression Rating Scale（HAMD）were employed to assess anxiety and depression in SLE patients,respectively.The Medical Outcome Study Short Form（SF-36）was utilized to evaluate HRQOL status in SLE patients.The improvement of anxiety,depression and HRQOL of SLE patients was evaluated by comparing the changes between 12 weeks and baseline.SPSS 21.0 and SAS 9.0 were employed to complete the data sorting and analysis.Results In the case-control study,the rs1190606 polymorphism was statistically related to SLE susceptibility(dominant model:OR=1.547,95%CI=1.207-1.984,P=5.75×10^-4;recessive model:OR=1.469,95%CI=1.009-2.139,P=0.045).After multiple corrections by BH method,the association between rs1190606 and SLE susceptibility still existed(dominant model:P_BH=0.007);allelic analysis revealed that the minor alleles of 3 SNPs were associated with increased susceptibility to SLE,including rs1004903（allele A,OR=1.234,95%CI=1.010-1.507,P=0.039）,rs1190606(allele G,OR=1.374,95%CI=1.148-1.644,P=5.3×10^-4)and rs2273440（allele A,OR=1.233,95%CI=1.011-1.503,P=0.038）.After multiple corrections,the association between rs1190606 and SLE still existed(P_BH=0.004)and was more significant in the female subgroup(P_BH=0.001);in haplotype analysis,significant differences were found in the distribution of haplotype combinations“GAGAGGG”（P=0.017）and“GAGGGGG”（P=0.024）between the case group and the control group,but these differences failed to pass multiple corrections.Gender stratification analysis showed that haplotype combinations“GAGAGGG”(P_BH=0.015)and“GAGGGGG”(P_BH=0.006)were still associated with SLE susceptibility in female subgroup;the rs2273440 polymorphism was related to photosensitivity in SLE patients(dominant model:OR=0.576,95%CI=0.398-0.834,P_BH=0.032).No such association was found in gender stratified analysis,but rs1190605polymorphism was associated with photosensitivity in SLE patients in female subgroup(dominant model:OR=0.570,95%CI=0.387-0.839,P_BH=0.032);In the prospective study,we did not find the relationship between DYNC1H1 gene and GCs efficacy,anxiety,and depression in SLE patients.However,it was observed in HRQOL improvement analysis that rs11160668 was associated with role emotional（dominant model:P=0.016）and role physical（dominant model:P=0.047）,rs1190605 was associated with physical function（recessive model:P=0.030）and physical component summary（recessive model:P=0.046）,and rs1190606 was associated with social function（dominant model:P=0.034）.But These correlations disappeared after multiple corrections.Gender stratification indicated that rs11160668 was related to the improvement in bodily pain of male patients(dominant model:P_BH=0.011).In addition,CNV of DYNC1H1 gene was not detected in this study.Conclusions This study indicated that DYNC1H1 gene polymorphism was correlated with SLE susceptibility in Chinese Han population and the improvement in bodily pain in SLE patients,but not with GCS efficacy,anxiety,and depression.