This article is more than 5 years old. Information may no longer be current.
NOD2, ATG16L1 gene variants impact response to Crohn’s disease treatment
Click Here to Manage Email Alerts
Patients with NOD2- and/or ATG16L1-variant genotypes and Crohn’s disease were more likely to experience bacterial DNA translocation and relapse during treatment, according to recent results.
Researchers performed genotyping for variants of NOD2 (at single nucleotide polymorphism [SNP]-8, SNP-2 and SNP-13) and ATG16L1 (rs2241880) in 179 patients with Crohn’s disease (CD), along with 25 healthy controls. Levels of bacterial DNA (bactDNA), tumor necrosis factor-alpha, interferon gamma, IL-12p40, antidrug antibodies, infliximab and adalimumab also were assessed.
One or more of the evaluated variants were present in 76.4% of patients with active disease and 69% of patients with CD in remission, with an NOD2 variant observed in 41.8% of those with active disease and 41.2% of remissive patients, and the ATG16L1 variant observed in 55.8% of active CD cases and 60.2% of patients in remission.
BactDNA was present in 28.5% of patients with CD, including 44.2% of those with active and 23.5% with remissive disease (P=.01 for difference). The presence of bactDNA was associated with disease activity (OR=7.422; 95% CI, 1.69-32.596) and disease relapse within 6 months (OR=5.132; 95% CI, 1.764-14.926) via multivariate analysis.
BactDNA was significantly more common among participants with NOD2 variations: 30.7% of those with NOD2 alone and 60.4% of those with NOD2 and ATG16L1 variations, compared with 15.5% of those with ATG16L1 alone and 10.6% of those with neither. Multivariate analysis indicated significant associations between bactDNA and NOD2 (OR=5.117, 1.287-20.346 for NOD2 alone; OR=12.728, 3.738-43.344 for NOD2/ATG16L1 in combination) and ATG16L1 variations (OR=2.221, 1.394-5.118 for those with ATG16L1 alone) (95% CI for all).
Patients with NOD2 variants, both with and without ATG16L1 variants, had higher levels of TNF-alpha in response to bactDNA, and decreased trough levels of free anti-TNF-alpha and phagocytic and bactericidal activity. Increased dosage or dose frequency of therapy with biologicals also was significantly more common among participants with a NOD2 variant.
“Combined NOD2/ATG16L1 variant genotypes identify a patient subgroup with an increased risk of bactDNA translocation,” the researchers concluded. “This fact may, in turn, exacerbate the inflammatory response and is directly associated with disease activity and the risk of relapse in the short term. This … would favor the requirement for therapy intensification in patients with mutation on treatment with biologicals, who would probably be candidates for a different therapeutic strategy.”
Click Here to Manage Email Alerts