Functional dyspepsia susceptibility is associated with TGFB1 gene polymorphisms (RS4803455, RS1800469) in H pylori-negative Chinese population.

ABSTRACT

BACKGROUND: We previously published that altered expression of gastric TRPV1, BDNF, and peripheral cytokines was present in patients with functional dyspepsia. We herein examine whether genetic predisposition in altered biomarkers influences dyspeptic, sleep, and mood symptoms in patients with FD without previous infection. METHODS: Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic age- and sex-matched healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous H pylori infection, psychiatric illness, and recent use of NSAID or PPI were excluded. The genetic associations with dyspeptic symptoms, sleep quality, and mood symptoms were evaluated. Genetic polymorphisms in TRPV1, TGFB1, TNF, COMT, BDNF, IL6, IL8, IL10, and IL12 were analyzed. KEY RESULTS: Twenty-nine male FD patients and 104 female FD patients were age matched (±3 years) with 81 healthy subjects. All had postprandial distress syndrome (PDS) as predominant subtype (PDS 130, EPS 3). SNPs in TGFB1 showed significant associations in dyspeptic patients after age and sex adjustment [for RS4803455 in the codominant model (C/A, OR = 0.34 (0.18-0.65), P = .004); in the dominant model (genotype C/C vs C/A-A/A, OR = 0.42 (0.23-0.77), P = .004); and in the overdominant model (genotype C/C-A/A vs C/A, OR = 0.38 (0.21-0.70), P < .001)] [for RS1800469 in dominant model (genotype A/A vs A/G-G/G, OR = 0.52 (0.27-0.99), P = .043)]. A allele in RS4803455 was associated with higher HADS depression score (P = .05) and epigastric burning sensation(P = .01). CONCLUSIONS AND INFERENCES Our data showed that dyspeptic patients predispose genetic difference in TGFB1 which may influence the severity of dyspepsia.