Abstract
BackgroundGenetic and environmental factors contribute to the pathophysiology of irritable bowel syndrome (IBS). In particular, early adverse life events (EALs) and the catecholaminergic system have been implicated.AimsTo investigate whether catecholaminergic SNPs with or without interacting with EALs are associated with: 1) a diagnosis of IBS, 2) IBS symptoms and 3) morphological alterations in brain regions associated with somatosensory, viscerosensory, and interoceptive processes.MethodsIn 277 IBS and 382 healthy control subjects (HCs), 11 SNPs in genes of the catecholaminergic signaling pathway were genotyped. A subset (121 IBS, 209 HCs) underwent structural brain imaging (magnetic resonance imaging [MRI]). Logistic and linear regressions evaluated each SNP separately and their interactions with EALs in predicting IBS and GI symptom severity, respectively. General linear models determined grey matter (GM) alterations from the SNPs and EALs that were predictive of IBS.Results1) Diagnosis: There were no statistically significant associations between the SNPs and IBS status with or without the interaction with EAL after adjusting for multiple comparisons. 2) Symptoms: GI symptom severity was associated with ADRA1D rs1556832 (P = 0.010). 3) Brain morphometry: In IBS, the homozygous genotype of the major ADRA1D allele was associated with GM increases in somatosensory regions (FDR q = 0.022), left precentral gyrus (q = 0.045), and right hippocampus (q = 0.009). In individuals with increasing sexual abuse scores, the ADRAβ2 SNP was associated with GM changes in the left posterior insula (q = 0.004) and left putamen volume (q = 0.029).ConclusionIn IBS, catecholaminergic SNPs are associated with symptom severity and morphological changes in brain regions concerned with sensory processing and modulation and affect regulation. Thus, certain adrenergic receptor genes may facilitate or worsen IBS symptoms.
Highlights
Irritable bowel syndrome (IBS) affects approximately 10.5% of the population (6.6% of men and 14.0% of women).[1]
In a study of five adrenergic receptor genes, genotype frequences of Single nucleotide polymorphisms (SNPs) residing in the alpha adrenergic-β2 (ADRAβ2) and alpha adrenergic-1D (ADRA1D) receptor genes differed significantly between patients with interstitial cystitis, known as painful bladder syndrome and healthy controls.[9]
A previous study demonstrated that the genotype frequencies of ADRA1D and ADRAβ2 SNP were associated with bladder pain syndrome/interstitial cystitis (BPS/IC), a chronic visceral pain disorder which often coexists with IBS[9] and which shows similar brain changes as IBS
Summary
Irritable bowel syndrome (IBS) affects approximately 10.5% of the population (6.6% of men and 14.0% of women).[1] As currently defined, IBS likely represents a heterogeneous group of disorders presenting with a similar symptom pattern, which is characterized by abdominal pain, altered bowels habits and gastrointestinal (GI) symptom-specific anxiety.[2] Several studies suggest an interaction between genetic and environmental factors (including early adverse life events [EALs]) in the development of altered brain-gut interactions in IBS.[3,4,5,6]. Early adverse life events (EALs) and the catecholaminergic system have been implicated.
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