PT  - JOURNAL ARTICLE
AU  - Anne Hinks
AU  - Halima Moncrieffe
AU  - Paul Martin
AU  - Simona Ursu
AU  - Sham Lal
AU  - Laura Kassoumeri
AU  - Tracey Weiler
AU  - David N Glass
AU  - Susan D Thompson
AU  - Lucy R Wedderburn
AU  - Wendy Thomson
TI  - Association of the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene with response to methotrexate in juvenile idiopathic arthritis
AID  - 10.1136/ard.2010.146191
DP  - 2011 Aug 01
TA  - Annals of the Rheumatic Diseases
PG  - 1395--1400
VI  - 70
IP  - 8
4099  - http://ard.bmj.com/content/70/8/1395.short
4100  - http://ard.bmj.com/content/70/8/1395.full
SO  - Ann Rheum Dis2011 Aug 01; 70
AB  - Objectives Methotrexate (MTX) is the mainstay treatment for juvenile idiopathic arthritis (JIA), however approximately 30% of children will fail to respond to the drug. Identification of genetic predictors of response to MTX would be invaluable in developing optimal treatment strategies for JIA. Using a candidate gene approach, single nucleotide polymorphisms (SNPs) within genes in the metabolic pathway of MTX, were investigated for association with response to treatment in JIA cases. Methods Tagging SNPs were selected across 13 MTX metabolic pathway genes and were genotyped using Sequenom genotyping technology in subjects recruited from the Sparks Childhood Arthritis Response to Medication Study. Response to MTX was defined using the American College of Rheumatology (ACR) paediatric response criteria and SNP genotype frequencies were compared between the worst and best responders (ACR-Ped70) to MTX. An independent cohort of US JIA cases was available for validation of initial findings. Results One SNP within the inosine triphosphate pyrophosphatase gene (ITPA) and two SNPs within 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (ATIC) were significantly associated with a poor response to MTX. One of the ATIC SNPs showed a trend towards association with MTX response in an independent cohort of US JIA cases. Meta-analysis of the two studies strengthened this association (combined p value=0.002). Conclusions This study presents association of a SNP in the ATIC gene with response to MTX in JIA. There is now growing evidence to support a role of the ATIC gene with response to MTX treatment. These results could contribute towards a better understanding of and ability to predict MTX response in JIA.