Dataset Information

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

ABSTRACT: BACKGROUND/AIMS:There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. METHODS:We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G->A), preproghrelin (3056T->C), Leu72Met (408C->A), Gln90Leu (3412T->A) and G-protein ?3 (825C->T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. RESULTS:There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. CONCLUSIONS:The Leu72Met (408C->A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients.

SUBMITTER: Yamawaki H

PROVIDER: S-EPMC4288091 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

Yamawaki Hiroshi H Futagami Seiji S Shimpuku Mayumi M Shindo Tomotaka T Maruki Yuuta Y Nagoya Hiroyuki H Kodaka Yasuhiro Y Sato Hitomi H Gudis Katya K Kawagoe Tetsuro T Sakamoto Choitsu C

Journal of neurogastroenterology and motility 20150101 1

<h4>Background/aims</h4>There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification.<h4>Methods</h4>We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) sc ...[more]

PMID: 25540946

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Project description:BackgroundIt remains controversial as to whether delayed gastric emptying in functional dyspepsia is associated with a specific symptom pattern, and it is unknown if gastric emptying in functional dyspepsia is a driver of impaired health related quality of life (HRQOL). We aimed to evaluate the relationship between functional dyspepsia symptoms, gastric emptying, and HRQOL.MethodsUS patients (n=864; mean age 44 years (range 18-82); 74% female) with functional dyspepsia, as defined by Rome II criteria, were enrolled into one of four clinical trials. All patients had a baseline scintigraphic assessment of gastric emptying of an egg substitute meal, and the trials were stratified on this assessment. Delayed gastric emptying was defined as having at least 6.3% residual volume at four hours. A total of 290 (34%) patients had delayed gastric emptying. HRQOL was assessed by the SF 36 and Nepean dyspepsia index (NDI).ResultsPostprandial fullness was independently associated with delayed gastric emptying but the association was weak (odds ratio (OR) 1.98 (95% confidence interval (CI) 1.02, 3.86); p=0.04). No independent association was seen with epigastric pain, early satiety, nausea, or bloating. Mean SF 36 physical composite score (PCS) was 42.3 (95% CI 41.6, 43.0) and the mean SF 36 mental composite score (MCS) was 46.8 (95% CI 46.0, 47.5); both mean scores were significantly lower than age and sex adjusted national norms of 50 (p<.0001). Female sex, increasing age, and higher symptom scores for fullness, epigastric pain, and nausea were each independently associated with decreased PCS scores (all p<0.05). Higher baseline nausea symptom score, lower gastric emptying rates at one hour, and lower body mass index were associated with decreased MCS (all p<0.05). Female sex, epigastric pain, and nausea, but not gastric emptying, were associated with an impaired score on the NDI. However, the magnitude of the significant associations were all small.ConclusionsIn patients with functional dyspepsia selected for a clinical trial programme, gastric emptying did not usefully stratify them symptomatically. Quality of life of patients with functional dyspepsia enrolled in this clinical trial programme was significantly impaired but this was not explained by delayed gastric emptying.

Project description:Background: Yeokwisan, a standardized herbal formula, has exhibited clinical benefit for patients suffering from refractory functional dyspepsia (FD) in Korea since 2016. However, data about the mechanism of action of this formula are yet not available. Aim of the study: To evaluate and explore the effects of Yeokwisan on gastric emptying, a major symptom of functional dyspepsia, and its underlying mechanisms of action using a mouse model. Materials and methods: BALB/C mice were pretreated with Yeokwisan (100, 200, and 400 mg/kg, po) or mosapride (3 mg/kg, po) for 5 days and then treated with loperamide (10 mg/kg, ip) after 20 h of fasting. A solution of 0.05% phenol red (500 μL) or diet of 5% charcoal (200 μL) was orally administered, followed by assessment of gastric emptying or intestinal transit. Plasma acyl-ghrelin (ELISA), C-kit (immunofluorescence and western blotting), nNOS (western blotting) and gastric contraction- and ghrelin-related gene/protein expression levels were examined in stomach and small intestine tissues. Results: Loperamide injection substantially delayed gastric emptying, while Yeokwisan pretreatment (especially 200 and 400 mg/kg Yeokwisan) significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of phenol red retained in the stomach (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The levels of plasma acyl-ghrelin and expression of gastric ghrelin-related genes, such as growth hormone secretagogue receptor (GHSR), ghrelin-O-acyltransferase (GOAT), adrenergic receptor β1 (ADRB1) and somatostatin receptor (SSTR), were significantly normalized (p < 0.05 or 0.01) by Yeokwisan (400 mg/kg). Yeokwisan (400 mg/kg) significantly tempered the loperamide-induced alterations in the c-kit and nNOS levels (p < 0.01) as well as the expression of contraction- and ghrelin-related genes, such as 5-HT4 receptor (5-HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK), in the stomach, but not in the small intestine. Conclusion: The present results showed the clinical relevance of Yeokwisan, in treating FD, especially in promoting gastric emptying but not small intestinal transit. The main mechanisms corresponding to these effects may involve the modulation of the ghrelin pathway and activation of interstitial cells of Cajal in stomach tissue.

Dataset Information

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

Publications

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

Similar Datasets

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