A82 A BACH2 GENE VARIANT IS ASSOCIATED WITH POST-OPERATIVE RECURRENCE OF CROHN’S DISEASE

ABSTRACT: Abstract

Background

Crohn’s disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in over half of the patients following their initial operation. Although many genetic loci are implicated in Crohn’s disease, few have been associated with post-resection recurrence.

Aims

To identify genetic factors that predict recurrence of CD following intestinal resection.

Methods

A cohort of Crohn’s disease subjects who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence. Genotype was assessed at eight loci associated with adaptive immunity (SMAD3, IL10RB, IL15RA, BACH2, IL12B, IL18RAP, IFNGR2, and JAK2). Univariate and multivariate survival analyses were performed using a log-rank test and Cox-proportional hazard model, respectively.

Results

191 Crohn’s disease subjects with 11.2 years mean post-operative follow-up were included. 46% experienced a surgical recurrence. Factors associated with increased incidence of recurrence included male gender(p=0.05), and shortened time to first intestinal surgery(5.0 vs 7.3years p=0.03), while inflammatory disease behaviour was associated with a lower chance of repeat surgery(p<0.01). Of the loci assessed on multivariate analysis, homozygosity for a risk allele at BACH2 (rs1847472) was significantly associated with disease recurrence(HR-1.24 CI-1.00–1.54 p<0.05).

Conclusions

We identify BACH2 as a susceptibility locus for post-operative recurrence of Crohn’s disease in our cohort. BACH2 is critical in the differentiation and function of T-cells, as a regulator of B-cell activity, and is associated with several dysregulated immunologic phenomena. Its identification as a risk locus in post-operative Crohn’s disease recurrence suggests a potential role for regulatory T cells, effector T cells, humoral immunity, and immunologic memory in the development of this disease process.

Funding Agencies

CIHR

SUBMITTER: Laffin M 

PROVIDER: S-EPMC6508141 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature