Association Study Of Semaphorin-3A And Semaphorin-7A Gene Single Nucleotide Polymorphisms With Genetic Susceptibility To Systemic Lupus Erythematosus

Objective Studies have demonstrated that semaphorin-3A(Sema3A)and semaphorin-7A(Sema7A)may play an important role in the development of autoimmune diseases.Our previous study also showed that the expression level of Sema3 A was decreased in patients with systemic lupus erythematosus(SLE).There is no study on the expression level of Sema7 A in peripheral blood of patients with SLE.The purpose of this study was to investigate the association between Sema3 A and Sema7 A gene single nucleotide polymorphisms(SNPs)and SLE susceptibility,and to analyze the effects of these two gene variants on their expression levels.Methods In this study,a case-control design was used.495 SLE patients and 493 healthy controls were selected.The SLE cases were recruited from the Department of Rheumatology of the First Affiliated Hospital of University of Science and Technology of China,and the Department of Rheumatology of the First Affiliated Hospital of Anhui Medical University.The case diagnosis was established according to the revised SLE classification criteria of the 1997 American College of Rheumatology.The healthy control were selected from the First Affiliated Hospital and the Second Affiliated Hospital Health Center of Anhui Medical University.Genotyping was performed using improved multiple ligase detection reaction(i MLDR)to analyze two SNPs of Sema3A gene(rs12707682,rs7804122)and three SNPs of Sema7 A gene(rs2075589,rs28362930,rs741761).Plasma Sema3 A and Sema7 A levels were measured in 84 patients with SLE by enzyme linked immunosorbent assay(ELISA).Results The genotype frequency and allele frequency of rs12707682,rs7804122,rs2075589,rs28362930,rs741761 were not significantly different between case group and control group(all P>0.05).Genetic models such as dominant models and recessive models were analyzed,and there was no significant difference between the two groups(all P>0.05).Further analysis of the relationship between genes polymorphisms and the main clinical manifestations of SLE were also performed.There was significant association between the Sema3 A locus rs7804122 allele frequency and whether SLE had oral ulcers(?~2= 4.111,P= 0.043).There was significant difference between Sema7 A locus rs2075589 allele frequencies in SLE with or without hematological disorder(?~2= 5.274,P= 0.022);rs28362930 genotype and allele frequencies in SLE with discoid rash were lower than those without(?~2= 6.810,P = 0.033,?~2= 5.073,P= 0.024);The allele frequencies of SLE patients with renal lesions were lower than those without(?~2= 3.967,P= 0.046);The allele frequencies of SLE patients with hematological disorder were higher than those without(?~2= 4.927,P= 0.026).The genotype and allele frequencies of rs741761 polymorphisms were significantly different in SLE patients with discoid rash than those without(?~2= 7.817,P= 0.020,?~2= 5.581,P= 0.018,respectively).Among SLE patients with arthritis,genotype and allele frequencies were significantly lower compared with patients without(?~2= 11.464,P= 0.003,?~2= 7.738,P= 0.005,respectively).In haplotype analysis,four main haplotypes(CA,CG,TA,TG)of Sema3 A gene and five main halpotypes(AAC,AGC,GAC,GGC,GGT)of Sema7 A gene had no significant differences between case group and control group(all P>0.05).No significant differences in plasma Sema3 A and Sema7 A levels were detected in SLE patients with different genotypes.Conclusions In brief,Sema3 A and Sema7 A SNPs are not associated with SLE genetic susceptibility,but may related to some specific clinical phenotype of this disease.Further studies are necessary to explore the exact role of Sema3 A and Sema7 A gene in SLE.