Association Between Gene Polymorphism Of TAGAP And Rheumatoid Arthritis

ObjectiveRheumatoid arthritis(RA) is an autoimmune disease that affects0.5%～1%of the population worldwide and is characterized by inflammation of the synovial joints. It is known that genetic and environmental factors play an important role in the disease, but the pathogenesis remains unknown. TAGAP(T-cell activation GTPase activating protein), which is involved in T-cell activation, has been implicated in RA risk in European and Africa American, however, no study has been done in Han Chinese population. In this study, we sought to examine the relationship between gene polymorphism of TAGAP and RA risk in Han Chinese population.MethodsThree candidate SNPs in regulatory regions of TAGAP (rs212389, rs1738074and rs4709267) were analyzed in60patients with RA and40healthy controls with the PCR-RFLP-sequencing method. Genotype and allele frequencies were compared, then Pairwise linkage disequilibrium (LD) and haplotype construction were performed to detect the relationship between TAGAP and RA, including each subset.Results(1) The loci rs4709267did not meet the Hardy-Weinberg equilibrium; There was no significant difference in rs212389genotype and allele frequencies between RA and the normal controls(P>0.05); rs1738074G allele frequency in RA was significantly lower than in normal controls (39.17%vs53.75%, OR=1.805,95%CI1.018～3.199, P=0.042),but the difference disappeared after the RA group was stratified by sex and age respectively(P>0.05).(2)No significant difference was detected of rs1738074genotype and allele frequencies between each RA subset (RF-positive, RF-negative, anti-CCP-positive, anti-CCP-negative) and normal controls(P>0.05).(3) The difference of Disease activity score (DAS28)and bone erosion of RA among each genotype of rs1738074was not significant either(P>0.05).(4) LD between rs212389and rs1738074was low (r2=0.000). United of the two SNPs, we got four haplotypes:TA, TG, CA and CG. The haplotype CA was not found in RF-negative RA and anti-CCP-negative RA. the haplotype CG frequency was lower in RA than in normal controls(2.0%vs9.2%, OR=0.202,95%CI0.045～0.908, P=0.022),however, this difference was detected only in RF-positive RA and anti-CCP-positive RA.Conclusionsrs1738074was a potential susceptibility loci of RA in Han Chinese population, but rs212389was not. The genotype of rs1738074was not significant associated with disease activity of RA patients. The haplotype CG was a protective factor of RA, maybe only in the RF-positive RA and anti-CCP-positive RA, and the haplotype CA was not found in the RF-negative RA and the anti-CCP-negative RA. Therefore, this study may provides an evidence that RF-positive RA and anti-CCP-positive RA was genetically distinct from RF-negative RA and anti-CCP-negative RA.