Serum Levels And Gene Polymorphisms Of Angiopoietin 2 In Systemic Lupus Erythematosus Patients

Objective:This study aims to discuss association between serum Angiopoietin2（Ang2）levels,Ang2 gene polymorphisms and systemic lupus erythematosus（SLE）susceptibility.Finish of this study may reveal the potential of serum Ang2 as a biomarker for SLE,the relationship between Ang2 and SLE pathogenesis,and provide a scientific basis for discovery of new therapeutic targets for SLE according to Ang2.Methods:This study has two parts.In the first part,serum Ang2 levels of58 SLE patients and 95 healthy controls was detected.Association of serum Ang2 levels with SLE clinical,experimental parameters was analyzed.Then,another independent study was adopted to verify the potential of serum Ang2 to distinguish SLE cases from other rheumatic diseases cases,including 90 SLE,90 rheumatoid arthritis（RA）,90 osteoarthritis（OA）,90 Gout,37 sjogren’s syndrome（SS）and 35 ankylosing spondylitis（AS）patients.In the second part,Ang2 rs12674822,rs1823375,rs1868554,rs2442598,rs3739390 and rs734701polymorphisms were genotyped using Kompetitive Allele Specific PCR（KASP）.SPSS 17.0 and Graphpad prism version 5.01 software were used for statistical analysis.Results:（1）Ang2 levels in SLE cases were higher than those of healthy volunteers（P<0.001）.Subgroup analysis showed that serum Ang2 levels were associated with fever and rash in SLE patients（P=0.027;P=0.013）.No correlation was detected between serum Ang2 concentration and SLEDAI（r_s=-0.092,P=0.490）.Receiver operator characteristic curve（ROC）presented a potential of serum Ang2 to distinguish SLE cases from normal controls（AUC:0.907,95%CI:0.856～0.958）.（2）When we validated serum levels of Ang2 in SLE patents and other rheumatic diseases patients,serum Ang2 concentrations in SLE patients were higher than those of RA,OA,Gout,SS and AS patients（all P<0.001）.Compared with RA,OA,Gout,SS and AS patients,serum Ang2had ability to distinguish SLE patients.The AUC were 0.745,0.719,0.927,0.821,0.894,respectively.（3）Frequencies of genotype and allele of rs12674822 were significantly different between SLE patients and healthy controls(P_BH<0.006;P_BH=0.018).Distribution of genotype and allele of rs1868554 were significantly different between SLE patients and healthy individuals(P_BH=0.034;P_BH=0.014).Frequency of G allele of rs3739390 was lower in SLE patients(P_BH=0.006).（4）Ang2 rs12674822 polymorphism was associated with risk for SLE in recessive model（OR:0.474,95%CI:0.325～0.690）.In the co-dominant model,TT and TA genotypes reduced the risk of SLE（OR:0.572,95%CI:0.364～0.898;OR:0.625,95%CI:0.430～0.908）.Ang2 rs1868554 polymorphism was associated with risk for SLE in dominant model（OR:0.607,95%CI:0429～0.858）.Individuals carrying CC genotype of rs3739390 had a lower risk for developing SLE（OR:0.539,95%CI:0.360～0.808）.TT genotype of rs734701 polymorphism reduced the risk of SLE（OR:0.580,95%CI:0.366～0.991）.（5）Genotypes distribution of rs12674822 polymorphism was correlated to hypocomplementemia in lupus patients(P_BH=0.024).Frequencies of genotypes of rs1823375 polymorphism was associated with anti-ds DNA（+）in SLE cases(P_BH=0.012).Allele distribution of rs3739390 was correlated to SLE patients with anti-ds DNA（+）and hematuria(P_BH=0.036;P_BH=0.018).（6）No significant association between serum Ang2 concentrations and genotypes distribution were observed for rs12674822,rs1823375,rs1868554,rs2442598 and rs734701（P=0.751;P=0.800;P=0.995;P=0.614;P=0.976）.Conculsion:（1）Serum Ang2 levels were elevated in SLE patients,correlating to fever and rash,and may be a biomarker for SLE.（2）Ang2 gene polymorphisms were related to SLE risk.（3）Ang2 gene polymorphisms may not affect serum Ang2 levels.