| Objective: To investigate the frequency and distribution characteristics of Single nucleotide polymorphisms(SNPs) of peptide arginine deaminase4-94(rs2240340) and peptide arginine deaminase4-104 (rs1748033) in rheumatoid arthritis(RA) and study the association between PADI4-94, PADI4-104 SNPs and RA susceptibility, as well as RA disease activity, anti-CCP antibodies, PADI4, anti-PADI4 antibodies. To detect serum anti-PADI4 antibodies and PADI4 levels in RA group and healthy control group and analyze the association with clinical indexs and explore the role and significance of serum PADI4 in the pathogenesis of RA.Methods: PCR-LDR was used to identify the gene and genetype of 116 rheumatoid arthritis patients and 100 healthy control and gene or genotype frequencies was calculated.The presence of anti-PADI4 antibodies, PADI4 and anti-CCP antibodies levels were examined by enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 100 patients with RA, 23 patients with other rheumatic diseases, and 24 healthy control. Chi-squared test was used to identify the significance.Results:1)The distribution of PADI4-94 and PADI4-104 genotypes among RA group and healthy control group did not significantly deviate from that expected by Hardy-Weinberg equilibrium (P>0.05)(χ~2 = 1.760, P = 0.184;χ~2 = 1.191, P = 0.275).2)The genotypes of PADI4-94 and PADI4-104 were analysed by Genemapper software, and got three haplotypes, AA, AG and GG respectively.3)PADI4-94 allele A,G and A/A, G/G and A/G genotype frequencies in RA group/ healthy control were 0.460/0.392, 0.540/0.608, 0.204/0.186, 0.283/0.402 and 0.513/0.412, respectively. There was no significant difference between the two groups (χ~2=1.996, P=0.157;χ~2=3.407, P=0.182). PADI4-104 allele A,G and A/A, G/G and A/G genotype frequencies in RA group/healthy control were 0.412/0.345, 0.588/0.655, 0.150/0.144, 0.327/0.454 and 0.522/0.402, respectively. There was no significant difference between the two groups (χ~2=1.937, P=0.164;χ~2=3.780, P=0.151).4)There were no significant difference between PADI4-94/PADI4-104 genotypes and ESR, DAS28 score, CRP, anti-CCP antibodies, PADI4, and anti-PADI4 antibodies (P>0.05).5)The titres of anti-PADI4 antibodies in RA group/other rheumatic group/healthy control group were (50.58±70.10)IU/ml, (24.69±37.62)IU/ml, (9.16±8.43)IU/ml respectively. The titres of anti-PADI4 antibodies in RA group was significantly higher than in other rheumatic diseases and healthy control (F = 5.47, P = 0.005).6)The prevalence of anti-PADI4 antibodies in RA patients (47%) was significantly higher than in other rheumatic diseases and healthy control(P<0.05). Anti-PADI4 antibodies diagnostic sensitivity and specificity with RA were 43%, 92% respectively.7)The correlation analysis showed that there was no association between anti-PADI4 antibodies and DAS28 scores,anti-CCP antibodies (r=-0.025,P=0.82;r=-0.058,P=0.60).8)The positivity rate for anti-PADI4 antibodies in RF-negative,AKA-negative and anti-CCP antibodies-negative RA patients was 50% 43% and 60% respectively.9)The levels of serum PADI4 in RA group, other rheumatic group, healthy control group were (620.10±259.82)ng/ml, (404.41±195.38)ng/ml, (522.19±142.40) ng/ml respectively. The levels of serum PADI4 in RA group was significantly higher than in other rheumatic diseases and healthy control (F=8.75,P<0.001).10)The correlation analysis showed that PADI4 were associated with DAS28 score, ESR(r=0.24,P=0.03; r=0.23, P=0.03). However, no associations were found between PADI4 levels and anti-cyclic citrullinated peptide (CCP), anti-PADI4 antibodies and CRP(r=0.02, P=0.83; r=0.-0.17, P=0.10; r=0.14, P=0.18).Conclusion:1)The SNPs of PADI4-94(rs2240340) and PADI4-104(rs1748033) in Chinese RA population was seen, but they were not the susceptibility genotypes of RA.2)serum anti-PADI4 antibodies has high diagnostic value in RA,especially in RF-negative,AKA-negative and anti-CCP antibodies-negative RA diagnosis. PADI4 may be a pathogenic antigen for RA and play an important role in RA pathogenesis and pathological processes.3)PADI4 which associated with disease severity involved in the RA pathogenesis and may be a RA pathogenic antigen. |
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