Author/Editor		Gabor, Urška; Repnik, Katja; Potočnik, Uroš
Title		Association of polymorphisms and expression of selected genes with response to treatment of crohn's disease patients with adalimumab
Type		članek
Source		In: Proceedings Ljubljana : Genetic Society of Slovenia
Publication year		2014
Volume		str. 53-59
Language		eng
Abstract		Crohn's disease (CD) is an autoimmune disorder of unknown etiology. Currently, the greatest potential for successful management of the disease is exhibited by biological therapeutics, including adalimumab (ADA). Pharmacogenetic studies concerning ADA, however, are still in an early stage. The aim of our study was to determine whether there was a correlation between response to treatment with ADA and selected single nucleotide polymorphisms (SNPs) as well as expression of selected genes in Slovenian CD patients. Selected SNPs and genes have shown a strong association with CD in previous studies, are involved in drug metabolism, associated with immune response and inflammation or with related complex diseases. Genotypes for selected SNPs were obtained from "Immunochip" microarray. Gene expression was measured at weeks 0, 4, 12, 20 and 30 after initiation of treatment using real-time polymerase chain reaction. Comparison of patients' demographic data showed a significantly lower percentage of smokers amongst patients with good response compared to patients with poor response (p=0.042). Association analysis for rs10919563 and rs2241880 showed that good responders have significantly different frequency of G/G genotype (87.5% and 25.0%) in week 30 (p=0.045 for rs10919563 and p=0.025 for rs2241880) compared to poor responders (65.0% and 55.0%). We have determined a difference in expression of SLC22A4, PSMD3, AHSA2, RPRD2 and PUS10 between good and poor responders prior to treatment. In three genes (ATG16L1, RPRD2 and PUS10) expression was significantly changed relatively to week 0 throughout the treatment. The most statistically significant results were obtained for ATG16L1, with a p-value ranging from 1.0%10-6 to 2.2%10-18 (week 12). When comparing gene expression between good and poor responders according to IBDQ values, we found statistically significant differences between the groups for ATG16L1 and SLC22A5 in week 12. This study identified new pharmacogenomic biomarkers, which could be helpful in establishing a more tailor-made approach for CD treatment with fewer side effects.
Descriptors		Crohn Disease genetics