Format

Send to

Choose Destination
Aliment Pharmacol Ther. 2009 Aug 15;30(4):375-84. doi: 10.1111/j.1365-2036.2009.04057.x. Epub 2009 Jun 3.

Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease.

Author information

1
Department of Gastroenterology, Guy's & St. Thomas' NHS Foundation Trust, London, UK.

Abstract

BACKGROUND:

Azathioprine (AZA) pharmacogenetics are complex and much studied. Genetic polymorphism in TPMT is known to influence treatment outcome. Xanthine oxidase/dehydrogenase (XDH) and aldehyde oxidase (AO) compete with TPMT to inactivate AZA.

AIM:

To assess whether genetic polymorphism in AOX1, XDH and MOCOS (the product of which activates the essential cofactor for AO and XDH) is associated with AZA treatment outcome in IBD.

METHODS:

Real-time PCR was conducted for a panel of single nucleotide polymorphism (SNPs) in AOX1, XDH and MOCOS using TaqMan SNP genotyping assays in a prospective cohort of 192 patients receiving AZA for IBD.

RESULTS:

Single nucleotide polymorphism AOX1 c.3404A > G (Asn1135Ser, rs55754655) predicted lack of AZA response (P = 0.035, OR 2.54, 95%CI 1.06-6.13) and when combined with TPMT activity, this information allowed stratification of a patient's chance of AZA response, ranging from 86% in patients where both markers were favourable to 33% where they were unfavourable (P < 0.0001). We also demonstrated a weak protective effect against adverse drug reactions (ADRs) from SNPs XDH c.837C > T (P = 0.048, OR 0.23, 95% CI 0.05-1.05) and MOCOS c.2107A > C, (P = 0.058 in recessive model, OR 0.64, 95%CI 0.36-1.15), which was stronger where they coincided (P = 0.019).

CONCLUSION:

These findings have important implications for clinical practice and our understanding of AZA metabolism.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center