Association Study Of Reproductive Factors,MALAT-1 Gene Variants And Their Interaction Effects With Female SLE

Background and ObjectiveSystemic lupus erythematosus（SLE）is a chronic inflammatory disease characterized by loss of immune tolerance to autoantigens,which occurs mostly in women of childbearing age.Abnormal expression of lnc RNA is closely related to the pathogenesis of SLE,and lnc RNA metastasis-associated lung adenocarcinoma transcript 1（MALAT-1）plays an important role in organ pathological changes and reproductive system tumors closely related to sex hormones.Previous studies have suggested that early or irregular menarche age and history of abortion may be associated with the incidence of SLE,but the results are controversial.Therefore,we aimed to explore the relationship between MALAT-1 gene variation and SLE susceptibility,analyze the role of reproductive factors and MALAT-1 gene interaction in the pathogenesis of SLE,in order to explain the cause of female predilection for SLE from a new perspective,and provide a new basis for the prevention and control of this disease.MethodsThis study was divided into three stages,all using a case-control design.In the first stage,quantitative real-time polymerase chain reaction（q RT-PCR）was used.It was used to detect MALAT-1 expression in peripheral blood mononuclear cells（PBMCs）of 101 SLE patients and 98 healthy controls.In the second stage,improved multiple ligase detection reaction（i MLDR）technology was used to explore the association of SNP（rs11227209,rs4102217,rs591291,rs619586）of MALAT-1 gene with the genetic susceptibility and clinical manifestations of SLE.In the third stage,unconditional logistic regression was used to analyze the relationship between reproductive factors and SLE.At the same time,logistic regression analysis,crossover analysis and generalized multifactor dimensionality reduction（GMDR）were used to explore the effect of the interaction between genes and reproductive factors on the incidence of SLE.ResultsIn the first stage,MALAT-1 expression was detected in 101 SLE cases and 98PBMCs of healthy control population,and it was found that the expression level of PBMCs in SLE cases was higher than that in healthy control population,and the difference was statistically significant（Z=-4.272,P<0.001）.In the second stage,the genotypes and alleles frequencies of rs11227209,rs4102217,rs591291,rs619586 in 532 SLE cases and 529 healthy controls were detected,but no significant difference were observed between the two groups（P>0.05）.The distributions of the dominant model,recessive model and additive model of rs11227209,rs591291,rs619586 genotypes in the two groups were not statistically different（P>0.05）.In the recessive model at rs4102217,GC and GG genotypes had a higher risk of SLE（χ~2=3.883,P=0.049,OR=1.017,95%CI:1.000-1.035）,but for the rs4102217 locus in the additive model and the dominant model,no significant difference was found between the two groups（both P>0.05）.The allele frequency of rs4102217 was associated with oral ulcers（χ~2=4.381,P=0.036）;the allele frequency of rs591291 was associated with erythema butterfly（χ~2=4.470,P=0.035）.The genotypes and allele frequencies of rs11227209 and rs619586 were not statistically different in SLE patients with or without clinical manifestations（T nephropathy,discoid erythema,arthritis,oral ulcers,nervous system abnormalities,butterfly erythema,photosensitivity,serositis,immunology,all P>0.05）.In the third stage,we used unconditional logistic regression analysis and found that the early age of menopause may be a risk factor for the onset of SLE.Using logistic regression analysis,it was found that there was an interaction of rs4102217*rs591291 in the pathogenesis of SLE,but no gene-gene interaction was found when using GMDR analysis.The crossover analysis showed that there were significant differences between the rs591291 genotype TT co-delivery history,the rs591291 TT co-delivery history,and the rs4102217 GC genotype GC co-delivery history.However,in logistic regression and GMDR analysis,we did not find any interaction between genes and reproductive factors.ConclusionThis study found that the expression level of MALAT-1 in PBMCs of SLE patients is higher than that of healthy controls.The rs4102217 polymorphism of MALAT-1 gene is associated with susceptibility to SLE,and the allele frequency of rs591291 is associated with erythema butterfly.Early age of menopause may be a major risk factor for SLE.MALAT-1 rs4102217*rs591291 multiplicative model interaction is associated with the onset of SLE.Individuals with history of menopause,childbirth and MALAT-1 rs591291,rs4102217 gene variants are associated with the risk of SLE.