| ObjectiveSystemic lupus erythematosus is a complex disease with multiple organ disorders due to compromised immune system.DNA damage inducible transcript 4（DDIT4）gene is related to the response of cells to various stressors（such as hypoxia,energy consumption,etc.）,the most prominent is that it can inhibit mammalian target of rapamycin activity,and thus participate in the regulation of various cellular processes.Recent findings suggest that the DDIT4 gene is associated with autoimmune diseases,but its role in SLE remains unclear.This study aimed to investigate the association between DDIT4 gene single nucleotide polymorphisms（SNP）and SLE heritability and phenotype,and whether the expression level of this gene is different between different subgroups,as well as the association of DDIT4 gene SNP with clinical parameters of SLE,so as to provide new clues for further revealing the etiology of the disease.MethodsThis study adopted a case-control study design,including 592 SLE patients and587 healthy controls.The first part,using the improved multiple ligase detection reaction（iMLDR）for genotyping and analysis of DDIT4 gene single nucleotide polymorphisms（SNP）sites（rs877767,rs8316,rs4747241）)and genetic susceptibility to SLE as well as clinical features.In the second part,we selected 99 SLE patients and98 healthy controls from the above research subjects,and real-time quantitative polymerase chain reaction was used to detect the expression of DDIT4 gene in peripheral blood mononuclear cells（PBMCs）.The expression level of the gene was analyzed to analyze the difference in the expression level of the gene between different research groups,and to explore the relationship between the gene expression level and clinical phenotype and laboratory indicators.Results（1）The genotypes and allele frequencies of three loci（rs877767,rs8316, rs4747241）in the DDIT4 gene had no significant difference between the two groups（all P>0.05）,and the different genetic models（dominant model,Recessive model and additive model,etc.）also had no statistical difference between the two groups（both P>0.05）.In addition,the genotype and allele frequency distribution of the locus rs877767 did not differ statistically between different clinical manifestations.However,the distribution of allele frequency of rs8316 and the genotype frequency and allele frequency of rs4747241 were significantly different in SLE patients with or without oral ulcers（（?）~2=5.715,P=0.017,（?）~2=8.783,P=0.012,（?）~2=9.897,P=0.002）.（2）There was no significant difference in the expression level of the DDIT4 gene in PBMCs between SLE cases and healthy controls（P>0.05）.In addition,the association between DDIT4 expression levels and clinical manifestations and laboratory measures was also not statistically significant（all P>0.05）.ConclusionsThe polymorphisms of the DDIT4 gene（rs877767,rs8316,rs4747241）were not associated with the genetic susceptibility of SLE,and the expression level of this gene in PBMCs was not statistically different between the case group and the control group.The rs4747241 polymorphism is associated with oral ulcers in SLE patients. |
