Genetic polymorphism in ATG16L1 gene is associated with adalimumab use in inflammatory bowel disease
Background: The role of single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease (IBD) is gaining interest. With the advent of novel therapies, personalized treatment in IBD is a future goal. We wondered whether IBD-associated SNPs are able to predict response to anti-TNFα treatment. Methods: Data on treatment use and primary response, loss of response and side effects to anti-TNFα treatments were retrieved for 570 IBD patients. rs13361189 (IRGM), rs10210302 (ATG16L1), rs2066844, rs2066845, rs2066847 (NOD2), rs35873774 (XBP1), rs11175593 (LRRK2), rs11465804 (IL23R), rs2301436 (CCR6), rs744166 (STAT3) and rs4821544 (NCF4) SNP status were determined. Results: No associations were found between genetic variants of the LRRK2, CCR6, IL23R and NCF4 genes and response to anti-TNFα. For NOD2 and XBP1 associations were found, however, these associations were not strong enough to survive multiple testing corrections. Strikingly, patients carrying the ATG16L1 T300A variant were more likely to be treated with adalimumab, even after correction for disease phenotype, disease behavior and age (p = 0.004, OR 2.8, CI 1.6-5.0). Conclusions: Genetic polymorphisms in the known IBD-associated gene ATG16L1 correlate with requirement of treatment, suggesting a different IBD disease phenotype in these patients. Further investigation will need to elucidate the implications of these findings and identify the underlying disease characteristics.
|Keywords||Anti-TNFα, ATG16L1, Crohn's disease, Genetics, Inflammatory bowel disease, Ulcerative colitis|
|Persistent URL||dx.doi.org/10.1186/s12967-017-1355-9, hdl.handle.net/1765/103408|
|Journal||Journal of Translational Medicine|
Nuij, V.J.A.A, Peppelenbosch, M.P, Woude, C.J. (C. J.), & Fuhler, G.M. (2017). Genetic polymorphism in ATG16L1 gene is associated with adalimumab use in inflammatory bowel disease. Journal of Translational Medicine, 15(1). doi:10.1186/s12967-017-1355-9