Association Between Rheumatoid Arthrltis And Single Nucleotide Polymorphisms Of PADI4 In Han People In Hebei Province â…¡

Objective: Rheumatoid arthrltis (RA) is a common chronic inflammatory and autoimmune disease which mainly affects synovial joint. Environmental factors and genetic factors play a role in the occurrence and the course of development of disease. The research for susceptibility gene can clarify the pathogenesis of RA, and may be an effective indicator of diagnosis, treatment and prognosis. The present study was undertaken in order to investigate the association of peptidylarginine deiminase 4 (PADI4 ) genetic single nucleotide polymorphism and rheumatoid arthritis in Han people in Hebei Province, China, and analysis the level of anticyclic citrullinated peptide antibody (anti-CCP) impacted by PADI4, to provide the evidence for early diagnosis, therapy and prevention of RA.Methods: This hospital-based case-control study included 105 RA patients and 96 healthy controls. All the individuals were collected from Han people living in Hebei region and were randomly selected. The genotype and allele frequencies of PADI4 gene polymorphisms (padi4₉2) were analyzed by PCR-RFLP sequencing method. Then we Integrated the results of existing padi4₉4, padi4₁04 SNPs and the levels of serum anti-CCP we compared the genotype and allele frequencies between patients and controls. The analysis of linkage disequilibrium and haplotype construction were performed.Results:1 The distribution of padi4₉2 genotypes include healthy control group and case group did not significantly deviate from that expected by Hardy-Weinberg equilibrium (P>0.05). The genotypes and alleles distribution of the padi4₉2 exist significant difference between RA case group and healthy control group. OR 0.4148 ( 95%CI=0.2254-0.7635 ),1.5758(95%CI=0.9025-2.7512),1.7500(95%CI=0.8094-3.7835), respectively. Genotypes distribution and alleles frequencies of padi4₉2 didn't show notable difference between i Han people in Hebei Province and in Japanese, Korean and English (P>0.05).2 The combined effect of padi4₉2,padi4₉4 and padi4₁04 SNPs was analyzed by SHEsis snd Genehunter software, and got three haplotypes, CCC,GTT and GCC, respectively. The haplotypes distribution of the three SNPs of padi4 exist significant difference in both RA case group and healthy control group. This analysis of haplotypes revealed that haplotype of PADI4 was a risk factor for RA. OR 0.634(95%CI=0.425-0.946),1.306(95%CI=0.864-1.975),4.286(95%CI=1.274-14.424), respectively.3 Put RA case in accordance with functional PADI4 gene haplotypes ,it is divided into three groups. After a homogeneity of variance test, we test whether or not there is difference in each group at age of onset. The result didn't show notable difference between these each groups (p>0.05).4 Put RA case in accordance with functional PADI4 gene haplotypes , it is divided into three groups. An examination is carry out to find whether or not there is contact between patients'gender between each group by Chi-square test. The result didn't show notable difference between these each groups (p>0.05).5 Put RA case in accordance with functional PADI4 gene haplotypes , it is divided into three groups. After a homogeneity of variance text, we text whether or not there is the different level at anti-CCP antibody in each group. The result did not show notable difference between these each groups (p>0.05).6 Put RA case in accordance with functional PADI4 gene haplotypes, it is divided into three groups. We do an examination to test whether or not there is contact berween each group at the classification of RA disease by Chi-square test. The result did not show notable difference between these each groups (p>0.05).Conclusions:1 The results showed that the genotypes and alleles distribution of the padi4₉2 exist significant difference in both RA cases and controls. And it shows that PADI4₉2 polymorphism and susceptibility to RA is associated.2 United of PADI4₉2, PADI4₉4, PADI4₁04 SNPs,we got three haplotypes, CCC,GTT and GCC respectively by Linkage disequilibrium analysis method. The results show that CCC haplotypes with RA is a negatively correlated with RA, and GCC haplotypes is positively correlated with RA. This haplotypes maybe the protective factor or risk factor of RA. But there is no significant difference between the main functional haplotypes and RA patient's onset age, it is also at the same between the functional haplotypes and RA patient's gender and anti-CCP antibody levels.3 Although the PADI4 functional haplotypes and RA is contacted, we did not find it have significant relationship in the course of RA patients and RA clinical symptoms.