The role of genetics in the pathophysiology of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease
Gastroesophageal reflux disease (GERD) is a condition in which reflux of
gastric content into the oesophagus results in mucosal injury and/or bothersome
symptoms. Approximately 15-20% of the general population experiences typical
reflux symptoms as heartburn and/or regurgitation at least weekly (1). The
presence of GERD symptoms is accompanied by a decrease in health-related
quality of life and an increase of healthcare costs due to frequent specialist
visits and prescription of chronic medication (2). GERD can be subdivided in
patients with mucosal abnormalities such as oesophagitis, so called erosive
reflux disease (ERD), and patients with no mucosal abnormalities at upper
endoscopy, so called non-erosive reflux disease (NERD).

Pathophysiology
The pathophysiology of GERD is multifactorial. Factors predisposing to an
excessive amount of gastroesophageal reflux have been identified, such as
alteration of the esophagogastric junction by the presence of a hiatus hernia
(3), which is in turn influenced by obesity (4). Independent of severity of
esophageal acid exposure, patients report a wide range of symptom severity and
symptom frequency suggesting changes at the mucosal level influencing the
perception of reflux. Possible important factors are the presence of visceral
hypersensitivity (5), and dilated intercellular spaces (6). However, the exact
mechanisms of symptom generation remain to be elucidated.

Genetics in GERD
Epidemiologic studies suggest a genetic component in the pathophysiology of
GERD. The presence of typical reflux symptoms is higher among family members of
GERD patients (7,8). Additionally, twin studies show an increased concordance
of GERD among monozygotic compared to dizygotic twins and estimated that
heritability accounted for up to 30% of the liability to GERD in that
population (9,10). A recent study found an association between GERD and the
heterozygous genotype of the C825T allele of the G-protein B3 subunit, coding
for a receptor frequently present in the neural brain-gut axis which is
associated with intracellular signal transduction (11). The polymorphism had
previously been associated with visceral hypersensitivity in functional
dyspepsia, suggesting a possible general genetic susceptibility for visceral
hypersensitivity.
These findings support further research aimed at identifying genetic
abnormalities underlying the pathophysiology of GERD, thereby possibly
generating new targets for therapy.

To identify genetic risk factors associated with GERD.

The study design is prospective and observational. DNA of subjects will be
obtained by drawing one sample of whole blood.

Venapuncture:
A single venapuncture for the withdrawal of whole blood is a safe procedure and
very frequently performed in the clinical setting. There is no serious risk
attached. A small complication is a puncture haematoma, for which no treatment
is necessary. Patients can respond to venapuncture with a vasovagal collaps,
therefore blood shall be drawn in a special chair in semirecumbent position.