Association Study Of PER2 And NCOA3 Gene Single Nucleotide Polymorphisms With Genetic Susceptibility To Systemic Lupus Erythematosus

AbstractObjectiveSystemic lupus erythematosus(SLE)is a prototypic autoimmune rheumatic disease characterized by immune-complex deposition,aberrant immune regulation and chronic inflammation.Studies have demonstrated that period 2(PER2)and nuclear receptor coactivator 3(NCOA3)may exert critical roles in the development of autoimmune diseases.Our study aimed to explore the associations between PER and NCOA3 gene polymorphisms and the susceptibility of SLE.MethodsA total of 492 SLE patients and 493 healthy controls were included.We recruited SLE cases from the Department of Rheumatology of the First Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China.We used Genotyping techniques(SNPscan TM)to assess the correlations between four SNPs of PER2(rs10929273,rs11894491,rs36124720,rs934945)and three SNPs of NCOA3(rs6066374,rs6094723,rs6125048)and the genetic susceptibility and clinical manifestations of SLE.ResultsBetween SLE patients and healthy controls,no significant difference was found in the genotypes and allele frequencies of rs10929273,rs36124720,rs934945,rs6066374,rs6094723 and rs6125048,respectively(all P>0.05);no significant difference was observed in the genotypes frequencies of rs11894491 between the two groups,however,we found significant difference in the allele frequencies of rs11894491(?~2=4.716,P=0.030,OR=1.230,95%CI:1.020-1.482).No significant difference was found in the genotypes of rs10929273,rs36124720,rs934945,rs6066374,rs6094723 and rs6125048under implicit model,explicit model and additive model between the two groups,respectively(all P>0.05).Additionally,under explicit model,there was significant difference in the genotypes of rs11894491 between SLE patients and healthy controls(?~2=5.233,P=0.022,OR=1.343,95%CI:1.043-1.729),but no significant difference was found under implicit model and additive model(all P>0.05).The genotypes and allele frequencies of rs36124720 are associated with light sensitiveness(?~2=11.374,P=0.003;?~2=9.856,P=0.002).We did not observe significant differences in the genotypes and allele frequencies of rs10929273,rs934945,rs6066374,rs6094723,rs6125048 and rs11894491 between SLE patients with/without kidney disease,discoid rash,arthritis,mouth ulcers,nervous system abnormality,butterfly erythema,light sensitiveness,immunology abnormality serositis and hematology abnormality,respectively(all P>0.05).ConclusionsThere is no significant correlation between the polymorphisms of rs10929273,rs934945,rs6066374,rs6094723 and rs6125048 of PER2 and NCOA3 and the susceptibility or clinical manifestation of SLE.The genotypes and allele frequencies of rs36124720 are associated with light sensitiveness.And there are significant correlations between the polymorphisms of rs11894491 in PER2 gene and the susceptibility of SLE,but no significant relationship between the polymorphisms of rs11894491 in PER2 gene and clinical manifestations of SLE.