O-019 YI Genetic Predictors of Quality of Life Post Ileal Anal Pouch Anastomosis for Ulcerative Colitis

Abstract

Total proctocolectomy and Ileal Pouch Anal Anastomosis (IPAA) for ulcerative colitis (UC) allows for the resection of diseased rectum and colon whilst preserving continence. Procedure outcomes and patient satisfaction are varied and difficult to predict preoperatively. This study aimed to determine demographic, operative and, most uniquely, genetic predictors of patient satisfaction with IPAA by evaluating 4 distinct categories: bowel symptoms, emotional wellbeing, social wellbeing and systemic symptoms using modified established quality of life questionnaires (the Modified Pouchitis Score and IBDQ (Inflammatory Bowel Disease Questionnaire)). Two hundred six IPAA patients identified from our IBD Biobank were mailed modified, pouch specific IBD questionnaires. Patient demographics and operative details were recorded. Genotyping using a custom designed microarray with 307 IBD and/or colorectal cancer (CRC) associated Single Nucleotide Polymorphisms (SNPs) was performed. Response variables were divided into high/low values based on their respective median values. Fisher's exact and Mann-Whitney U tests were used with the categorical and continuous explanatory variables respectively. Logistic regression with a Bonferroni correction was used for the SNP analysis. One hundred forty-two (86 male) patients responded (69%). Mean age at diagnosis was 31.8+/−.9 years. Average pouch duration was 10.1 +/−.5 years. One hundred four colectomies were performed electively with 13 resections for cancer/dysplasia. Covariates associated with symptom and wellbeing scores are listed in Table 1. A diagnosis of pouchitis, intermittent urgency and/or cramping and intermittent pyrexia were significantly associated with worse scores in every category. Smoking was associated with worse bowel and systemic symptoms and lower social wellbeing scores (P = 0.0029, 0.0062 and 0.02). More severe bowel symptoms and poorer emotional scores were reported by patients with less time between diagnosis and colectomy (6.6 versus 9.4 years, P = 0.04 and 0.05). Poorer emotional scores were seen in those diagnosed at a younger age (47.4+/− 12.4 versus 53.7 +/− 11.7) and in those with pouchitis of any degree (P = 0.04). The TNFSF14 associated SNP, rs2279627 was associated with poorer scores in overall quality of life and in each individual category. Significance was retained after correction in the overall quality of life, bowel symptom and emotional wellbeing categories (P = 0.033, 0.033 and 0.046). TNFSF14 plays a role in T cell differentiation and is associated with both UC and CD. Two SNPs, rs7837328 and rs7014346, associated with the POU5F1gene, were significantly associated with emotional wellbeing (P = 0.00002, 0.0066 corrected and P = 0.00014, 0.046 corrected). POU5F1 (also known as OCT4) plays a critical role in maintaining stem cell pluripotency, has a known role in CRC and has not previously been associated with IBD. 1) Pouchitis, urgency and/or cramps and intermittent fevers significantly impacted all aspects of quality of life in UC-IPAA patients 2). Smoking and pouchitis have the most significant impact, particularly on bowel and systemic symptoms respectively. 3) Potential genetic predictors of overall quality of life, bowel symptoms and, most interestingly, emotional wellbeing in this patient cohort were associated with the TNFSF14 and POU5F1B genes. 4) Patients diagnosed with IBD at an older age and who had a longer duration between diagnosis and colectomy were more likely to have a better emotional quality of life.