Abstract
BackgroundCorticotropin-releasing hormone (CRH) acts mainly via the CRH receptor 1 (CRH-R1) and plays a crucial role in the stress-induced pathophysiology of irritable bowel syndrome (IBS). Several studies have demonstrated that variants of the CRH-R1 gene carry a potential risk for depression, but evidence for an association between CRH-R1 genotypes and IBS is lacking. We tested the hypothesis that genetic polymorphisms and haplotypes of CRH-R1 moderate the IBS phenotype and negative emotion in IBS patients.MethodsA total of 103 patients with IBS and 142 healthy controls participated in the study. Three single-nucleotide polymorphisms of the CRH-R1 gene (rs7209436, rs242924, and rs110402) were genotyped. Subjects' emotional states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-rating Depression Scale.ResultsThe TT genotype of rs7209436 (P = 0.01) and rs242924 (P = 0.02) was significantly more common in patients with IBS than in controls. Total sample analysis showed significant association between bowel pattern (normal, diarrhea, constipation, or mixed symptoms) and the T allele of rs7209436 (P = 0.008), T allele of rs242924 (P = 0.019), A allele of rs110402 (P = 0.047), and TAT haplocopies (P = 0.048). Negative emotion was not associated with the examined CRH-R1 SNPs.ConclusionThese findings suggest that genetic polymorphisms and the CRH-R1 haplotypes moderate IBS and related bowel patterns. There was no clear association between CRH-R1 genotypes and negative emotion accompanying IBS. Further studies on the CRH system are therefore warranted.
Highlights
Impact of stress on human life is getting more recognized all over the world
Exogenous administration of Corticotropin-releasing hormone (CRH) exaggerates central [9,15] and gastrointestinal [9] responses in irritable bowel syndrome (IBS) patients, while peptidergic CRH antagonists reverse these phenomena [16,17]. These findings suggest that CRH plays a major role in the pathophysiology of IBS
We investigated the association between variation in three CRH receptor 1 (CRH-R1) single-nucleotide polymorphisms (SNPs) and the presence of IBS or negative emotion in patients with IBS
Summary
Impact of stress on human life is getting more recognized all over the world. A hallmark of the stress response is the activation of the autonomic nervous system and hypothalamo-pituitaryadrenal (HPA) axis [1]. The organism needs the normal stress hormone response to survive difficult situations, and inadequate or excessive adrenocortical and autonomic function is deleterious for health and survival [1]. The individual stress response via the corticotropin-releasing hormone (CRH) system is highly likely to affect the features of many stress-related disorders [2]. CRH binds to CRH receptors that initiate the stress response leading to release of adrenocorticotropic hormone (ACTH) from the anterior pituitary lobe and simulation of serum cortisol secretion from the adrenal cortex [4]. Activation of CRH receptors stimulates adenylate cyclase activity increasing cyclic adenosine monophosphate (cAMP) levels in anterior pituitary corticotrophs resulting in ACTH release [6]. Corticotropin-releasing hormone (CRH) acts mainly via the CRH receptor 1 (CRH-R1) and plays a crucial role in the stress-induced pathophysiology of irritable bowel syndrome (IBS). We tested the hypothesis that genetic polymorphisms and haplotypes of CRH-R1 moderate the IBS phenotype and negative emotion in IBS patients
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