Genome-Wide Association Study (GWAS) for the Infliximab Responsiveness in Korean Inflammatory Bowel Disease Patients

Inflammatory bowel disease (IBD) subdividing into Crohn's disease (CD) and ulcerative colitis (UC) is a chronic intestinal inflammatory disorder. Infliximab (IFX) as an anti-TNF-α has been prescribed for treatment of IBD patients. However, some patients show no response or a loss of response to this agent. In this study, we investigated to identify genetic variants associated with response to IFX. A total of 148 IBD patients from Yonsei University Health System who received IFX were classified according to subtypes of IBD except 12 patients unsuitable for this study. We also categorized the patients into three groups by IFX response; response (sustained response, loss of response), nonresponse. Whole exome sequencing (WES) was performed and identified on average 35,000 variants including silent, missense and nonsense mutation in each sample. We performed GWAS using the WES data to find out genetic variants associated with response to IFX. We identified only missense variants with suggestive evidence of association. In CD patients, AEBP1 (rs2537188) was associated with nonresponse and PLA2R1 (rs35771982, rs3749117) and IDO2 (rs10109853) were associated with loss of response. In UC patients, AMACR (rs10941112, rs3195676) was associated with loss of response. Furthermore, we will investigate in vitro study at the cellular level for the functional analysis of those genetic variants.