Association of distinct α2 adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders

• Published in: Gut Vol. 53; no. 6; pp. 829 - 837
• Main Authors: Kim, H J, Camilleri, M, Carlson, P J, Cremonini, F, Ferber, I, Stephens, D, McKinzie, S, Zinsmeister, A R, Urrutia, R
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.06.2004; BMJ; Copyright 2004 by Gut
• Subjects: 5-HT; 5-hydroxytryptamine (serotonin); a cytosine to guanine transversion at position 753 that changes amino acid 251 of the third intracellular loop of the α2A adrenoceptor from asparagine to lysine; Biological and medical sciences; CAP; chronic abdominal pain; cytosine to guanine transversion in promoter of α2A receptor protein; deletion in third intracellular loop of α2C adrenoceptor protein; FGID; functional constipation; functional diarrhoea; functional gastrointestinal disorders; Gastroenterology. Liver. Pancreas. Abdomen; genotype; IBS; IBS-C; IBS-D; Irritable Bowel Syndrome; irritable bowel syndrome phenotype; irritable bowel syndrome with predominant constipation; irritable bowel syndrome with predominant diarrhoea; Medical sciences; member 4; NET; norepinephrine transporter; odds ratio; Other diseases. Semiology; PCR; polymerase chain reaction; serotonin; serotonin transporter; serotonin transporter promoter; SERT; SERT-P; SLC6A4; solute carrier family 6 (neurotransmitter transporter; somatic symptom score; somatic symptoms; SoSc; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; α2A −1291 (C→G); α2ALys251; α2C Del 322–325; Functional; Symptomatology; Association; Serotonin; Digestive diseases; Intestinal disease; Gastrointestinal; Constipation; Polymorphism
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2003.030882

Background: The role of genetics in the phenotypic manifestations of irritable bowel syndrome (IBS) is unclear. Our aims were: (1) to compare the prevalence of polymorphisms of alpha 2 (α2) adrenoceptors, norepinephrine transporter, and serotonin transporter protein (soluble carrier protein member 4 (SLC6A4)) promoter in patients with lower functional gastrointestinal disorders (FGID) and in healthy controls; and (2) to test associations of these genetic variations with symptoms of IBS and high somatic symptom scores. Methods: Validated bowel and somatic symptom questionnaires characterised the phenotype: 90 with IBS constipation (IBS-C), 128 IBS diarrhoea, 38 IBS alternating bowel function, and 20 chronic abdominal pain. Logistic regression analyses assessed associations of different polymorphisms for α2 adrenoceptor and SLC6A4 with IBS or chronic abdominal pain phenotypes and high somatic score. Results: Two distinct polymorphisms independently appeared to be associated with the phenotype IBS-C: α2C Del 322–325 (odds ratio (OR) 2.48 (95% confidence interval (CI) 0.98, 6.28); p = 0.05) and α2A −1291 (C→G) (OR 1.66 (95% CI 0.94, 2.92); p = 0.08) relative to wild-type. Overall, the α2C Del 322–325 polymorphism (alone or combined with other polymorphisms) was also significantly associated with a high somatic symptom score (OR 2.2 (95% CI 1.06, 4.64); p = 0.03). Combinations of polymorphisms were also associated with high somatic scores. Conclusion: Functionally distinct α2A and α2C adrenoceptor and serotonin transporter polymorphisms are associated with constipation and high somatic symptoms in patients with lower functional gastrointestinal disorders, although the strength of the genetic contribution to the phenotype is unclear.