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Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis
Christopher J Moran1,2, Hailiang Huang3,4, Manuel Rivas3,4,5
1Division of Pediatric Gastroenterology, Hepatology, & Nutrition, MassGeneral Hospital for Children, Boston, Massachusetts, United States of America.
Plos One
|March 27, 2018
Summary
Common genetic variants in transporter genes do not influence mesalamine response in ulcerative colitis (UC) patients. Response to this UC treatment may depend on rare genetic factors or environmental influences like the gut microbiome.
Area of Science:
- Gastroenterology
- Pharmacogenomics
- Molecular Biology
Background:
- Mesalamine is a key treatment for ulcerative colitis (UC), acting topically.
- In vitro studies suggest intracellular transport is crucial for mesalamine's efficacy.
- The clinical impact of genetic variations in transport proteins on mesalamine response in UC remains unexamined.
Purpose of the Study:
- To investigate if genetic variants in cellular transport genes influence mesalamine treatment response in UC patients.
- To determine the clinical relevance of genetic variations in mucosal transport proteins for mesalamine uptake and efficacy.
Main Methods:
- Genotyping of UC patients (n=457) from a 6-week mesalamine clinical trial using genome-wide arrays.
- Analysis focused on common exome variants (minor allele frequency >5%) in cellular transport genes.
- Mesalamine response defined by Physician's Global Assessment (PGA) at Week 6; stringent quality control applied.
Main Results:
- No common variants in transporter genes were significantly associated with mesalamine response in UC.
- Genetic risk scores did not differ between responders and non-responders (p = 0.18).
- A trend towards mesalamine response was observed with genome-wide variants in ST8SIA5 (p = 1x10-5).
Conclusions:
- Common genetic variations in transporter genes do not appear to affect mesalamine response in adult UC.
- Mesalamine efficacy in UC may be influenced by rare genetic variations or environmental factors, including the gut microbiome.
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