Genetic Influences in Irritable Bowel Syndrome: A Twin Study

Mohammed, I; Cherkas, Lynn; Riley, Stuart; Spector, Tim D.; Trudgill, Nigel

doi:10.1111/j.1572-0241.2005.41700.x

Cited by 99 publications

(67 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The schizophrenia literature illustrates the usefulness of endophenotypes in genetic analyses of mental disorders (11) and in understanding these disorders at the cellular and molecular levels (2). As with those mental disorders, there is evidence from familial clustering and twin studies to support a heritable component in IBS (26), although this is somewhat controversial (31). Although our laboratory focuses predominantly on peripheral organ functions, investigation of genetic influences on brain structure or functions in the development of IBS using neuroimaging may provide further advances in understanding, as in schizophrenia (2).…”

Section: Discussionmentioning

confidence: 99%

Candidate genes and sensory functions in health and irritable bowel syndrome

Camilleri

Busciglio

Carlson

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Zinsmeister AR. Candidate genes and sensory functions in health and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 295: 219 -225, 2008. First published May 29, 2008 doi:10.1152/ajpgi.90202.2008.-Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including ␣2A (C-1291G), ␣2C (Del 332-325), GN␤3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GN␤3 was associated only with fasting GV; we did not detect associations between ␣2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GN␤3 with fasting GV may explain, in part, the reported association of GN␤3 with dyspepsia. adrenergic; serotonergic; GN␤3; SLC6A4; G protein; receptor ADRENERGIC MECHANISMS alter gastrointestinal reflexes involved in intestinal propulsion, coordinated motor activity in the small bowel and colon, and gastrointestinal tone and fluid secretion (12,46). Norepinephrine is also involved in control of pain including supraspinal inhibition of pain, e.g., due to a change in the behavioral state (37) including stress, which contributes to gut motility disorders (10).Among ␣2 receptors, the ␣2A subtype appears to be critically important for control of motor functions, such as gastrointestinal transit in mice (40) and colonic circular smooth muscle in canine colon (47). The ␣2 receptor agonist, clonidine, inhibits gastric and colonic tone, phasic contractility, and sensation in the rectum and colon in response to balloon distension in healthy humans (4, 43).Serotonergic (5-HT) mechanisms also alter gut absorptive, motor, and sensory functions via actions in the gut, spinal cord, and brain stem (27). Ligand-receptor interaction results in c...

show abstract

Section: Discussionmentioning

confidence: 99%

Candidate genes and sensory functions in health and irritable bowel syndrome

Camilleri

Busciglio

Carlson

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Because monozygotic twins share the exact same genetic code and dizygotic twins share half of the same genetic code, comparing concordance rates between monozygotic and dizygotic twins allows the opportunity to quantitate the contributions that genetics and environment each make to the development of the disease. Five twin studies demonstrate that the genetic contribution to IBS appears to range between 0 and 20% (8)(9)(10)(11)(12). The reasons for the heterogeneity in genetic liability estimates are not clear; they may represent true population-based differences, but are likely the result of methodological differences with respect to how IBS status was defined and how the information was collected.…”

Section: What Evidence Is There For An Ibs Gene?mentioning

confidence: 99%

The Genetics of Irritable Bowel Syndrome

Saito

Petersen

Locke

et al. 2005

Clinical Gastroenterology and Hepatology

View full text Add to dashboard Cite

Irritable bowel syndrome (IBS) is one of the most common diagnoses made by gastroenterologists and primary care providers alike, and yet the underlying mechanism remains poorly understood. Family and twin studies suggest that IBS may have a genetic basis. Several candidate gene association studies have been performed, but thus far, they have failed to clearly identify an "IBS gene." Epidemiological studies are needed to facilitate phenotype definition and identify relevant environment risk factors that will need to factor in gene and environment interactions in all future genetic studies. As genetic research in IBS is relatively nascent, much opportunity, as well as many challenges, exists in identifying the genes responsible for IBS.

show abstract

“…Regression analysis showed that the presence of IBS in the respondent's parents made a larger contribution to the risk of having IBS than did the presence of IBS in one's twin [24] , and a study with a United Kingdom twin database provided confirmation of the influence of social learning over heredity in the development of IBS [25] .…”

Section: Childhood Social Learning Effects On Childhood Illness Behaviormentioning

confidence: 91%

Social learning contributions to the etiology and treatment of functional abdominal pain and inflammatory bowel disease in children and adults

Levy

Langer

Whitehead³

2007

WJG

View full text Add to dashboard Cite

This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular emphasis is placed on randomized controlled trials, the majority of which are multi-modal in orientation, incorporating elements of cognitive behavioral therapy, social learning, and relaxation. Based on this review, we offer methodological and clinical suggestions: (1) Research investigations should include adequate sample sizes, long-term follow-up assessments, and a credible, active control group. (2) Standard gastrointestinal practice should include, when appropriate, learning opportunities for patients and family members, for example, instruction regarding the encouragement of wellness behavior.

show abstract

Genetic Influences in Irritable Bowel Syndrome: A Twin Study

Abstract: Genetic factors are of little or no influence on IBS where the predominant influences appear to be environmental.

Cited by 99 publications

References 20 publications

Candidate genes and sensory functions in health and irritable bowel syndrome

Candidate genes and sensory functions in health and irritable bowel syndrome

The Genetics of Irritable Bowel Syndrome

Social learning contributions to the etiology and treatment of functional abdominal pain and inflammatory bowel disease in children and adults

Contact Info

Product

Resources

About