Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis.
PLoS One
; 13(3): e0192806, 2018.
Article
em En
| MEDLINE
| ID: mdl-29579042
ABSTRACT
BACKGROUND AND AIMS:
Mesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these variants has not been studied. The aim of this study was to determine whether variants in genes involved in cellular transport affect the response to mesalamine in UC.METHODS:
Subjects with UC from a 6-week clinical trial using multiple doses of mesalamine were genotyped using a genome-wide array that included common exome variants. Analysis focused on cellular transport gene variants with a minor allele frequency >5%. Mesalamine response was defined as improvement in Week 6 Physician's Global Assessment (PGA) and non-response as a lack of improvement in Week 6 PGA. Quality control thresholds included an individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion for subjects with cryptic relatedness. All included variants met Hardy-Weinberg equilibrium (p>0.001).RESULTS:
457 adults with UC were included with 280 responders and 177 non-responders. There were no common variants in transporter genes that were associated with response to mesalamine. The genetic risk score of responders was similar to that of non-responders (p = 0.18). Genome-wide variants demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5).CONCLUSIONS:
Common transporter gene variants did not affect response to mesalamine in adult UC. The response to mesalamine may be due to rare genetic events or environmental factors such as the intestinal microbiome.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sialiltransferases
/
Colite Ulcerativa
/
Mesalamina
/
Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos