Associations Of RPEL1 And MiR-1307 Gene Polymorphisms With Disease Susceptibility And Glucocorticoid Efficacy In Chinese Systemic Lupus Erythematosus Patients

Object The main contents of this study were to investigate the relationship between RPEL1 and miR-1307 gene polymorphisms(rs4917385 and rs7911488)and Systemic Lupus Erythematosus in China.SLE)susceptibility,effect of Glucocorticoids(GCs)on SLE,association between anxiety and depression and Health-related Quality of Life(HRQOL),The effect of SNP rs7911488 on the expression level of miR-1307 gene was analyzed.Methods The study was carried out in three stages.Firstly,using a case-control study strategy,we collected basic information and whole blood samples from 500 patients with confirmed SLE and 500 healthy controls,and we selected the latest multiplex high-temperature ligase detection reaction(i MLDR)technique for genotyping: RPEL1:rs4917385(G/T)and miR-1307: rs7911488(A/G).In the second part of the prospective follow-up study,448 patients with SLE who met the inclusion requirements were followed up,with a total of 429 patients finally completing follow-up after 12 weeks.The HAMA and HAMD scales were used to assess the emotional well-being of patients with SLE.Improvement in anxiety and depression and HRQOL was assessed by change in scores at 12 weeks compared to baseline.In the third part,q RT-PCR was employed to gauge the miR-1307 expression in 37 SLE patients’ peripheral blood mononuclear cells to analyse whether the loci associated with the development of SLE affected the expression of the corresponding gene.Results The minor allele of rs7911488,G allele,related to decreased risk for SLE(OR=0.804,95%CI:0.666-0.972,P=0.024).But,significant correlation of the rs4917385 allele with SLE susceptibility fail to find(P=0.092).In the additive model,those carrying the variant rs7911488 G exhibited a lower risk of developing SLE than wild-type humans(OR=0.792,95%CI:0.651-0.963,P=0.020).No statistical association was found between rs7911488 and SLE susceptibility in other model.Four haplotypes consisting of rs4917385 and rs7911488 were associated with SLE(P<0.025).The allele frequencies of rs7911488 and rs4917385 are differentially present in SLE cases with lupus nephritis(LN)compared to non-LN patients(P=0.015),and were associated with lupus nephritis in SLE patients in both dominant and additive models(P<0.025).In prospective follow-up studies,both the associations of RPEL1 and miR-1307 gene polymorphisms with GCs efficacy did not reach statistical differences.rs4917385 and rs7911488 were both correlated with PF in the dominant model(rs4917385: OR=1.791,95%CI=1.192-2.693,P=0.005;rs7911488:OR=1.691,95%CI=1.136-2.541,P=0.010)rs4917385 was found in dominant models(OR=1.783,95%CI=1.133-2.806,P=0.012)and additive models(OR=1.509,95%CI=1.056-2.156,P=0.024)was statistically associated with anxiety symptoms in SLE patients.rs7911488 was associated with depressive symptoms in SLE patients in an additive model(OR=1.569,95%CI=1.073-2.294,P=0.020).In the dominant model,patients with risk genotypes and non-tea drinkers had the highest risk of anxiety(rs4917385 TT+GT: OR=3.635,P<0.001;rs7911488 GG+GA: OR=3.632,P<0.001)Compared with rs7911488 AA,the expression level of AG/GG genotype miR-1307decreased(P=0.035).Conclusion RPEL1 and miR-1307 gene polymorphisms(rs4917385 and rs7911488)might be related to SLE susceptibility in Chinese population.Additionally,the two polymorphisms were possibly associated with depression,anxiety,and HRQo L in Chinese SLE population.Meanwhile,rs7911488 can affect the expression level of miR-1307 gene in PBMCs of SLE patients.