Response to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile

Mediators of Inflammation
L M MedranoE Urcelay

Abstract

Substantial proportion of Crohn's disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276* G/rs3014866* C/rs724781* C/rs3006488* A; P = 0.05); G0S2 (rs4844486* A/rs1473683* T; P = 0.15); TNFAIP6 (rs11677200* C/rs2342910* A/rs3755480* G/rs10432475* A; P = 0.10); and IL11 (rs1126760* C/rs1042506* G; P = 0.07). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced ...Continue Reading

References

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Citations

Jun 8, 2017·Inflammatory Bowel Diseases·Soon Man YoonDermot P B McGovern
Oct 21, 2016·Inflammatory Bowel Diseases·Edward L Barnes, Robert Burakoff
Jun 21, 2017·The Pharmacogenomics Journal·T M Linares-PinedaM Á Calleja-Hernández
Aug 11, 2020·Journal of Pediatric Gastroenterology and Nutrition·Sara Salvador-MartínLuis A López-Fernández
Sep 29, 2020·Frontiers in Medicine·Raja AtreyaBritta Siegmund
Feb 25, 2021·Expert Review of Clinical Immunology·Ikram MezghicheElisabetta Bianchi

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Methods Mentioned

BETA
genotyping
PCR

Software Mentioned

Haploview

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