THU0438 Peptidylarginine Deiminase Polymorphisms Associated with Susceptibility to Tuberculosis

Background Anti–cyclic citrullinated peptide antibodies (as a serologic marker of RA) bind to citrulline residue which is now considered to play a pivotal role in various human diseases such as multiple sclerosis, various tumors, and many other infectious diseases. The hypothesis of the association between PADI4 gene and TB susceptibility was introduced, but didn’t identified. Therefore, we hypothesized that the diversity in PADI4 genes could affect susceptibility to tuberculosis in RA patients and preliminarily designed the association study of PADI4 polymorphisms in the patients with mycobacteria infection. Objectives To examine the possibility for single nucleotide polymorphisms of peptidylarginine deiminase 4 to discriminate who’s susceptible to active tuberculosis disease. Methods The study population consisted of 47 patients with bacteriological-confirmed tuberculosis, 35 patients with non-tuberculous mycobacterial disease, 50 rheumatoid arthritis patients and 83 healthy controls. Blood samples were collected before starting treatment for TB and NTM. All subjects were genotyped for three SNPs in PADI4, namely PADI489, PADI490, and PADI4104. In addition, antCCP antibodies were determined by enzyme-linked immunosorbent assay and rheumatoid factor was measured by the latex fixation test. Results In TB patients, the AG and CT genotypes for PADI4_89 and PADI490, respectively were significantly lower than those of control subjects. Adjusted odd ratiosfor PADI489 and PADI490 were 0.34 (p = 0.005). The frequencies of haplotypes and minor allele were not significantly different among groups. IgM RF-positive was observed in 42 patients with RA (84%), in 7 patients with TB (15.0%), in 5 patients with NTM (14%), and in 5 healthy controls (6%) (p < 0.0001). There were significant differences in the frequencies of the presence of antiCCP antibodies among groups: RA (88%), TB (8%), NTM (0%), and healthy controls (1%) (p < 0.0001) Conclusions This study showed that polymorphisms of PADI were associated with susceptibility to TB in a Korean population References Baronnet L, Barnetche T, Kahn V, Lacoin C, Richez C, Schaeverbeke T. Incidence of tuberculosis in patients with rheumatoid arthritis. A systematic literature review. Joint, bone, spine : revue du rhumatisme. 2011 May;78(3):279-84. PubMed PMID: 21273108. Epub 2011/01/29. eng. Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A, et al. Drug-specific risk of tuberculosis in patients with rheumatoid