Effect of Genetic Association With Functional Dyspepsia and Mood Disorders

Overview

Background: Functional dyspepsia (FD) is one of the commonest digestive disorders. The pathophysiology of functional dyspepsia is uncertain. Risk factors include genetics, gender, age, helicobacter pylori infection, etc. However, few reported the association of genetic contribution to the development of FD and mood disorder. Indication: Functional dyspepsia patients Study center(s): Prince of Wales Hospital, Hong Kong Aims: * To evaluate genetic factors on development of functional dyspepsia \& common mood disorders * To evaluate genetic factors on the severity of function dyspepsia \& mood disorders * To develop a diagnostic test for classification of functional dyspepsia by plasma ghrelin and serotonin expression * To collect sleep data for future use * To save blood sample for future retrospective diagnostic or genetic examination Study design: Case-control cross sectional study Number of subjects: Total of 1200 subjects (300 FD patients + 300 relatives of FD patients FDR) and (300 Controls + 300 FDR) Patient population: Functional dyspepsia patients age 18-60 Duration of study: 1 May 2012 - 30 April 2013 Primary variable(s): Genetic polymorphisms of targeted genes, plasma ghrelin and serotonin expression Secondary variable(s): FD global symptom assessment and symptom scores Number of visits: 1 Hypotheses: * Shared genetic factors contribute to the development of FD and common psychological disorders * FD patients contribute to suppression of plasma ghrelin and serotonin expression compared to healthy controls

Methods: All subjects will participate in (1) Demographic assessment, (2) Questionnaires administration and (3) Blood sample collection. The three steps must be completed within 2 weeks. 1. Demographic assessment * Demographic: age, gender * Anthropometric measurements: body mass index, height, weight * Smoke and drink habit * Comorbidity and medical history 2. Questionnaires administration * A combined functional gastrointestinal (GI) symptom questionnaire (FGISQ) based on recall of the past 7 days will be used for assessment all GI symptoms including regurgitation, heartburn, epigastric pain, postprandial fullness, abdominal pain, diarrhea, constipation etc. All questions use a 4-point (0-3) Likert scale. * FGI Screening Questionnaire (v.3, 20101011) for screening of functional gastrointestinal disorder according to Rome III criteria. The questionnaire incorporate a GERD diagnostic questionnaire GERDQ (Chinese version) * Hospital Anxiety and Depression Scale (HADS) for a self administered scale for seven covering depression and seven covering anxiety. * Psychological disorder: Patient Health Questionnaire (PHQ) will be used for screening of concomitant psychological disorder such as depression and generalized anxiety disorder. * The Epworth Sleepiness Scale, Pittsburgh sleep quality index, and General Sleep Quality Questionnaire to collect sleep data for future use. 3. Blood sample collection * Up to 20 ml of fasting blood sample will be collected for study aims 1-4. * Fasting glucose test will be performed for FD patients * Serology test of Hp status will be performed for healthy volunteers and all FDRs Subjects who had fasting glucose test or serology test performed within one year before study enrollment can be exempted from repeating the tests if they refuse to repeat the tests. In such cases, their previous test results will be recorded and used in this study. If the subjects are found to be positive as a result of Helicobacter pylori (Hp) serology test, a referral letter with prescription suggestion will be given to the subjects to seek proper medical care in the primary care setting. In current practice, Hp eradication is not mandatory for asymptomatic subjects. Laboratory work: Nine ml of blood will be used for the detection of biomarkers for functional dyspepsia through single nucleotide polymorphism (SNPs). The genotyping DNA will be isolated from whole blood samples by (FlexGene DNA kit, Qiagen). High-throughput genotyping will be performed on the serotonin 3A receptor polymorphism (rs1062613) and ghrelin CLOCK 3111C polymorphism (rs1801260). It will be analyzed by Applied Biosystems (ABI) 3730xl DNA Analyzer. Six ml of blood will be used for detection of plasma ghrelin and serotonin expression for development of diagnostic test in classification of functional dyspepsia by ELISA.