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Genetic polymorphism associated with poor outcomes following UC procedure
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Patients with a NOD2insC polymorphism are at greater risk for inflammatory complications following ileal pouch-anal anastomosis to treat ulcerative colitis, according to recent results.
Researchers evaluated clinical and genetic data from 714 Caucasian patients with ulcerative colitis who underwent ileal pouch-anal anastomosis (IPAA). Participants were grouped according to whether they did (n=118) or did not (n=487) have chronic pouchitis (CP) or a Crohn’s disease-like (CDL) phenotype (n=109) following treatment. DNA samples also were collected and single nucleotide polymorphism (SNP) genotyping was performed.
Negative outcomes from the procedure were associated with arthritis or arthropathy (P=.02), primary sclerosing cholangitis (PSC) (P=.009), and a longer time between ileostomy closure and study recruitment (P=.001). Patients with CP and CDL also were significantly more likely than those without CP to have the rs2066847 NOD2insC variant (OR=3.21; 95% CI, 1.38-7.47 for CP and OR=4.30; 95% CI, 1.90-9.77 for CDL). Another association was observed between increased variants at the NOD2 locus and increased risk for CDL compared with non-CP patients (OR=2.08; 95% CI, 1.31-3.50), but not compared with CP patients.
Multivariate analysis indicated that variants rs2066847 (NOD2insC), rs6557421 (NOX3) and rs836518 (DAGLB) were associated with procedure outcomes: The NOD2 variant increased risk for CDL (OR=13.51, 2.00-90.9), the NOX3 variant was protective against CP (OR=0.54, 0.31-0.94) and CDL (OR=0.35, 0.15-0.78) and the DAGLB variant was protective against CDL (OR=0.29, 0.12-0.67) compared with non-CP patients (95% CI for all).
Investigators established a multivariable risk model combining these genetic markers with other clinical and serological risk factors and calculated an OR of 2.72 (95% CI, 1.89-3.91) for patients without CP compared to those with CP and CDL, and an OR of 3.22 (95% CI, 2.12-4.89) for non-CP patients compared with those with CDL alone.
“Our results demonstrate that phenotypic characteristics, including PSC and arthritis, as well as several SNPs, are associated with pouch outcome after IPAA in individuals with UC,” the researchers concluded. “The co-occurrence of additional inflammatory disorders previously documented in [Crohn’s disease] and UC … with pouch complications suggest overlapping disease mechanisms may be important in the onset and propagation of inflammatory outcomes.”
Disclosure: See the study for a full list of relevant disclosures.
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