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News

Polymorphism associated with irritable bowel syndrome bowel habit subtypes

A recent issue of the American Journal of Gastroenterology identifies a tryptophan-1polymorphism associated with irritable bowel syndrome bowel habit subtypes.

News image

Alterations in 5-hydroxytryptamine (5-HT) signaling have been implicated as a factor contributing to the altered bowel habit of irritable bowel syndrome (IBS) patients.

Tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme in enterochromaffin cell 5-HT biosynthesis.

Dr Merchant and colleagues from Michigan, USA hypothesized that genetic variants affecting TPH1 gene expression might alter intestinal 5-HT bioavailability, and subsequently the propensity for distinct bowel habit subtypes in IBS.

In this study, the researchers assessed the only common TPH1 proximal promoter variant, and its association with bowel habit predominance in IBS.

Electrophoretic mobility shift assays were performed to assess whether the −347C/A-allele variant affects the DNA binding of nuclear factors.

The CC genotype was more prevalent in the IBS-D subtype
American Journal of Gastroenterology

Genotype distribution was determined for 422 IBS patients subtyped using the Rome III criteria and for 495 healthy controls recruited from 2 university medical centers.

Association with bowel habit was tested using a multinomial logistic regression model controlling for race, anxiety, depression, and study site.

The research team found that early growth response factor 1 (EGR-1) bound with higher affinity to a site comprising the minor A-allele of single-nucleotide polymorphism (SNP) −347C/A.

TPH1 genotype frequencies did not differ between IBS patients and controls overall.

The CC genotype was more prevalent in the IBS-D subtype than in the IBS-C, and IBS-M subtypes after adjusting for race and other covariates.

The researchers tested colonic biopsies from a small cohort of IBS patients from one center for higher TPH1 mRNA expression in samples with CC, and compared these with the CA genotype, but the results did not reach statistical significance.

Dr Merchant's team comments, "The TPH1 promoter SNP −347C/A differentially binds EGR-1 and correlates with IBS bowel habit subtypes, and possibly colonic TPH1 expression consistent with its role in modulating intestinal 5-HT signaling."

Am J Gastroenterol 2013; 108: 1766–1774
18 December 2013

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