P1307 Variant in Complement Factor B is associated with perianal disease in Ulcerative Colitis
Authors: Phillips J , Kumar R , Mortlock S , Lord A , Simms L , Croft A , Walker G , Radford-Smith G 
Published: January 2025

Background

Perianal disease is an increasingly recognised complication of ulcerative colitis (UC) (1). Variant rs4151651 in complement factor B (CFB) is associated with severe phenotype UC and, more recently, implicated in the pathogenesis of perianal Crohn’s disease (CD) (2, 3). In our previous work, we have shown the minor allele frequency (MAF) for the rs4151651 variant to be 0.03 for non-IBD affected control patients, 0.05 in patients with mild UC, and 0.13 in patients with severe phenotype UC (3).

Here, we aim to determine the MAF for the rs4151651 variant in UC patients with perianal disease.

Methods

Ulcerative colitis patients with perianal disease were identified from our extensive inflammatory bowel disease (IBD) biobank. Perianal disease was defined as perianal abscesses or fistulae (haemorrhoids and anal fissures were excluded). Appropriate consent was obtained from all participants (HREC/14/QRBW/323). Demographic and phenotypic data were collected, and UC diagnoses were confirmed by expert IBD pathologists through histological review. To further confirm accurate phenotyping of our UC cohort, and to distinguish it from CD, we also present MAF data from the NOD2 gene, where available. Genotyping was either previously performed by genome-wide association study (GWAS) analysis or performed using the rs4151651 single nucleotide polymorphism (SNP).

Results

Forty-one patients were identified. Baseline demographics and clinical characteristics are presented in Table 1. Phenotypically and histologically all patients had disease consistent with UC. The MAFs for the NOD2 variants rs2066844, rs2066845 and rs2066847 were 0.04, 0.01 and 0.01 respectively.

Eight patients had both a perianal abscess and a fistula, 1 patient had a perianal abscess only, and 33 patients had perianal fistulae only. Twenty-four patients in our cohort had a prior colectomy. The MAF for the rs4151651 variant in the 41 UC patients with perianal disease was 0.28. In the 21 patients who had extensive disease (E3), the MAF was 0.29. In the 24 patients who had a prior colectomy, the MAF was 0.30 (Figure 1).

Conclusion

The rs4151651 variant on the CFB gene is associated with perianal disease in UC patients. These findings align with prior studies linking the rs4151651 variant to a more severe UC phenotype. This SNP could be a valuable biomarker in predicting perianal complications for patients with severe UC undergoing colectomy and considering reconstructive (pouch) surgery.

References

1.Choi YS, Kim DS, Lee DH, Lee JB, Lee EJ, Lee SD, et al. Clinical Characteristics and Incidence of Perianal Diseases in Patients With Ulcerative Colitis. Ann Coloproctol. 2018;34(3):138-43.

2.Akhlaghpour M, Haritunians T, More SK, Thomas LS, Stamps DT, Dube S, et al. Genetic coding variant in complement factor B (CFB) is associated with increased risk for perianal Crohn’s disease and leads to impaired CFB cleavage and phagocytosis. Gut. 2023;72(11):2068-80.

3.Mortlock S, Lord A, Montgomery G, Zakrzewski M, Simms LA, Krishnaprasad K, et al. An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis. J Crohns Colitis. 2023;17(2):277-88.