Study On The Association Between Single Nucleotide Polymorphisms Of PTPN22 And Rheumatoid Arthritis In Han People In Hebei Province

Objective:Rheumatoid arthritis (RA) is a common autoimmune disease , based on arthrosynovitis, with chronic, persistent, invasive joint destruction which may lead to deformity, Although the etiology of RA is still obscure, heredity, infection, environment, hormone and their interactions contribute a lot to RA pathogenesis. It was reported that genetic factors accounted for 50%- 60% of the total susceptibility. The recent years, more and more ideas reached that single nucleotide polymorphisms(SNPs) is the most frequent variation of human genome,and screening the SNP associated with RA susceptibility becoming more and more appealing. The protein tyrosine phosphatase nonreceptor 22(PTPN22) gene encodes a lymphoid-specific protein tyrosine phosphatase (LYP), which takes part in the TCR pathway and plays an important role in negative control of T-cell activation. Our study is to investigate the association between PTPN22-1123G SNP and rheumatoid arthritis in Han people in Hebei province .Meanwhile, the correlation between PTPN22 SNP and other clinical index such as anti-MCV was studied to see its early diagnostic value and specificity for early diagnosis and therapy of RA.Methods: For a case-control study , the samples of 118 RA patients and 104 healthy controls were collected from the Third Hospital of Hebei Medical University. All the individuals were Chinese Hans living in Hebei region for more than 5 years without genetic relationship excluding other autoimmune diseases. The patients were diagnosed according to the criteria for the classification of RA by American Rheumatism association (1987)and the new criteria by ACR/EULAR(2009). The PTPN22-1123G>C SNPs were detected by PCR-RFLP method. According to the genotype of RA, we divided the patients into three groups, compare the distribution of PTPN22-1123G genotypes and alleles between case and control group, and research the association with other clinical characteristics .Results:1 The distribution of PTPN22 genotypes between case and control group did not significantly deviate from what expected by Hardy-Weinberg equili- brium (P>0.05).three genotypes of PTPN22-1123G>C were detected in Hebei Hans. The frequency of genotypes and alleles in cases are GG54.8%,GC36.5%,GG8.7%,G73.1%,C26.9% and in control are GG38.1%,GC50.0%,CC11.9%,G63.1%,C36.9%. Significant difference was found compared with people in Japan (P<0.05),but there was no significant difference compared with Guangdong and Shanghai(P>0.05).2 The genotypes distribution of PTPN22-1123G exist significant difference between RA and control group(X2=6.187,P=0.045). Compared with wild genotype GG, GC could increase the susceptivity of RA (P=0.018 ,OR=1.967,95%CI (1.118-3.459)).CC genotype did not increase the risk of RA(P=0.146,OR=1.970,95%CI (0.782-4.965)).3 The RA was divided into three subgroups according to the genotype, being tested either two groups for gender with chi-square method. The result did not show notable difference in ether two groups (P>0.05).We then compared either two groups at age of onset with one way ANONA test and found no significance (P>0.05).4 The RA patients was divided into RF+ and RF- group ,compared the genotype distribution between either group and control group by Chi-square test, The result showed notable difference in RF+ group(P<0.05).5 The RA patients was assigned to three groups according to genotypes of PTPN22-1123G and use One-Way ANONA to test the level of anti-MCV antibody in each group. The result did show significance in either two groups (P<0.05).6 The method of One-Way ANONA was used to compare the level of DAS28 in the three genotype groups. The result did not show significance in either two groups (P>0.05).7 The RA was put into two groups according to X ray injury, compared the genotype distribution of either group with control by Chi-square test, The result showed significant difference in X ray injury positive group(P<0.05).8 The level of anti-MCV was compared according to DAS28 score,X ray stage,course of disease and significance was found in X ray stage(P<0.05).Conclusion:1 The results showed that the genotypes and alleles distribution of PTPN22-1123G>C exist significant difference in Hebei Hans RA cases compared with health controls, which indicate that the SNPs may be a predisposing factor for RA. GC genotype may rise the odds of RA by 1.967,but CC genotype may not rise the risk ,which fit heterozygote advantage.2 The PTPN22-1123G>C SNP was associated with the presence of RF,which indicate mechanism for the susceptivity of RA.3 The PTPN22-1123G>C SNP was associated with X ray stage ,G >C ,may rise the risk to a bone damage .4 The anti-MCV may be used as a serology index for early diagnosis of RA and it may predict joint damage.The PTPN22 SNPs was highly associated with anti-MCV.5 The study suggest a new idea that combined detection of PTPN22-1123G>C SNP and anti-MCV may predict bone damage and show great value for earlier diagnosis and drug treatment of RA .