Impact Of Climate Factors And Climate-Gene Interaction On Systemic Lupus Erythematosus Patients’ Response To Glucocorticoids Therapy

Part 1 Impact of Climate Factors and Climate-gene Interaction on Glucocorticoids Efficacy of Systemic Lupus ErythematosusObjective Glucocorticoids(GCs)were the essential drugs for systemic lupus erythematosus(SLE).However,different patients differ substantially in their response to GCs treatment.Our current study aims at investigating whether climate factors and climate-gene interaction influence SLE patients’ response to therapy of GCs.Methods This study was based on a follow-up study,and SLE patients were collected from the First and Second Affiliated Hospital of Anhui Medical University.The climatic data were provided by China Meteorological Data Service Center.Follow-up studies were conducted on SLE patients meeting follow-up requirements.Systemic lupus erythematosus disease activity Index(SLEDAI)was used to evaluate the efficacy of GCs treatment.A total of 778 patients were included in the follow-up study of GCs efficacy.Among them,28 patients were lost to follow-up,and 750 patients completed the final follow-up.Blood samples were collected from647 patients,and the genotypes of TRAP1 and GR genes were detected by multiple SNa Pshot technology.logistic regression model,fork generation method and multifactor dimensionality reduction(MDR)were used to analyze the possible interactions.Results Compared with patients with autumn onset,the efficacy of GCs in patients with winter onset is relatively poor(ORadj=1.805,95%CIadj: 1.181-3.014,Padj=0.020).High mean relative humidity during treatment was a risk factor for the efficacy of GCs(ORadj=1.033,95%CIadj: 1.008-1.058,Padj=0.011),especially in female(ORadj=1.039,95%CIadj: 1.012-1.067,Padj=0.004).There was a significant interaction between low sunshine duration during treatment and TRAP1 gene rs12597773 on GCs efficacy(Recessive model: OR=3.442,95%CI:1.238-9.566,P=0.018).No evidence of significant interaction was found between climate factors and the GR gene polymorphism on the improved GCs efficacy in the additive model.Multiplicative interaction was found between humidity in the month prior to treatment and GR gene rs4912905 on GCs efficacy(Dominant model: OR=0.470,95%CI: 0.244-0.905,P=0.024).Conclusions Our findings suggest that climate variability influences SLE patients’ response to therapy of GCs.Interactions between climate and TRAP1/GR gene polymorphisms were related to GCs efficacy.The results guide the individualized treatment of SLE patients.Part 2 Impact of Climate Factors and Climate-gene Interaction on Improvement of Anxiety,Depression and HRQOL in Patients with Systemic Lupus ErythematosusObjective Our current study aims at exploring the effect of climate factors and their interaction with TRAP1 and GR gene polymorphisms on anxiety,depression and health-related quality of life(HRQOL)improvement in patients with systemic lupus erythematosus.Methods A total of 727 patients with SLE were included in the follow-up study for improvement of anxiety,depression,and HRQOL.T-test,chi-square test,logistic regression,and RCS model were used for statistical analysis.Logistic regression model,cross multiplication and multifactor dimension reduction(MDR)were used to analyze the possible interaction.Results Mean temperature,accumulated precipitation,and sunshine duration during treatment were significantly associated with improvements in MCS in SLE patients(ORadj=0.998,95%CIadj: 0.996-1.000,Padj=0.034;ORadj=0.986,95%CIadj:0.973-0.999,Padj=0.033;ORadj=0.991,95%CIadj: 0.985-0.998,Padj=0.010).Variability of air pressure and accumulated precipitation during treatment was associated with improvements in MCS(ORadj=1.014,95%CIadj: 1.001-1.027,Padj=0.033;ORadj=0.996,95%CIadj: 0.993-0.998,Padj=0.002).There was a nonlinear dose-response relationship between mean sunshine duration in the month prior to treatment and improvement of depression in SLE patients(Poverall=0.014,Pnon-linear=0.028).No significant association was found between onset seasons and the improvement of anxiety,depression and HRQOL in SLE patients(P>0.05).There was an interaction between climatic factors and TRAP1/GR gene polymorphism on the improvement of anxiety,depression and HRQOL in patients with SLE(P<0.05).Conclusion Climatic factors and their interaction with TRAP1 and GR gene polymorphisms play an important role in the improvement of anxiety,depression and HRQOL in SLE patients.