Genetic polymorphism in ATG16L1 gene is associated with adalimumab use in inflammatory bowel disease

Journal of Translational Medicine

Research

G. M. Fuhler¹  V. J. A. A. Nuij¹  C. J. van der Woude¹  M. P. Peppelenbosch¹ 

[1] Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, ‘s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands;

关键词: Inflammatory bowel disease;    Crohn’s disease;    Ulcerative colitis;    Genetics;    ATG16L1;    Anti-TNFα;   

DOI  :  10.1186/s12967-017-1355-9

 received in 2017-08-22, accepted in 2017-11-29,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsData 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.ResultsNo 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).ConclusionsGenetic 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.

【 授权许可】

CC BY   
© The Author(s) 2017