Mo1367 The Impact of JC Virus Antibody Testing on Treatment Selection in Patients With Crohn's Disease Who Are Primary Non-Responders to Infliximab: A Decision Analysis

Abstract

[Background] The small Maf proteins have emerged as crucial regulators of mammalian gene expression. Small Mafs do not contain an obvious transcriptional activation domain. However, it has been clear that small Maf proteins are regulated transcription factors, such as Nrf2 or Bach1. MafK, one of the small Maf proteins, is encoded by MAFK gene. Within 20kbp around MAFK gene, there are two linkage disequilibrium blocks, with above 0.05 of HWE p value and above 0.05 of minor allele frequency. In this study, we investigated an association between ulcerative colitis (UC) and each tag polymorphism, rs4268033G.A and rs3735656 (*910T.C), and the other one rs10226620 (*1506T.C). [Material and Methods] The studied population comprised 922 subjects, including patients with UC (UC cases, n=174), who were enrolled Fujita Health University Hospital, and the subjects without UC (controls, n=748). We employed the PCR-SSCP method to detect a gene polymorphism. [Results] In controls, mean age was 57.1 years old and male/female ratio was 438/310. In UC cases, mean age was 40.3 years old, mean age of onset was 33.0 years old and male/ female ratio was 98/76. The distributions of rs4268033, rs3735656 and rs10226620 in controls were 366GG, 324GA and 58AA (HWE p=0.25), 329TT, 346TC and 73CC (HWE p=0.21) and 345TT, 328TC and 75CC (HWE p=0.87) respectively, whereas the distributions in UC cases was 80GG, 66GA and 28AA, 80TT, 69TC and 25CC, 80TT, 72TC and 22CC, respectively. The genotype frequency of rs4268033 AA and allelic frequency of rs4268033A allele were significantly higher in UC cases than in controls (p=0.0013 and 0.045 by Fisher). By logistic regression analysis after adjustment for age and gender, rs4268033 AA and rs3735656 CC genotypes were significantly associated with the susceptibility to UC development (OR, 2.62; 95%CI, 1.54-4.48; p=0.0004 and OR, 1.79; 95%CI, 1.05-3.04; p=0.031, respectively). In addition, rs4268033 AA genotype was significantly associated with all phenotypes of UC (i.e. total colitis phenotype: OR, 2.58; 95%CI, 1.29-5.17; p=0.0073, not total colitis: OR, 2.39; 95%CI, 1.22-4.72; p=0.012). The rs3735656CC genotype was significantly associated with steroid-independent or not required phenotype of UC (OR, 1.87; 95%CI, 1.08-3.26; p=0.026). There was no significant association between rs10226620 and UC. [Conclusion] Our results provided the first evidence that MAFK gene polymorphisms were significantly associated with the susceptibility to UC development. In particular, rs4268033 was closely associated with an increased risk for the development of UC.