ABSTRACT
Irritable bowel syndrome is a frequent gastrointestinal disorder of unknown etiology. The serotonin transporter regulates the intensity and duration of serotonin signaling in the gut and is, therefore, an attractive candidate gene for irritable bowel syndrome. Previous studies investigating the 5-HTTLPR and Stin2 VNTR polymorphisms of the serotonin transporter have proved inconclusive. In this exploratory study we therefore expanded the search for a possible association of the serotonin transporter with irritable bowel syndrome to include not only the 5-HTTLPR and Stin2 VNTR length polymorphisms, but also the functional single nucleotide polymorphism rs25531. We genotyped 186 patients with irritable bowel syndrome and 50 healthy control subjects raging in age from 18 to 70 years. Carriers of the rare G allele of rs25531 had approximately threefold increased odds of irritable bowel syndrome compared with healthy controls (OR 3.3, 95% CI 1.1-9.6). Our findings suggest that further investigation of the possible role of the serotonin transporter in the etiology of IBS is warranted.
Subject(s)
Irritable Bowel Syndrome/genetics , Polymorphism, Single Nucleotide , Serotonin Plasma Membrane Transport Proteins/genetics , Adult , Case-Control Studies , Chi-Square Distribution , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Irritable Bowel Syndrome/ethnology , Male , Middle Aged , Odds Ratio , Phenotype , Risk Assessment , Risk Factors , WashingtonABSTRACT
CONTEXT: Polymorphisms of the serotonin transporter gene (SERT) have been associated with mental illness. In people with long-term medical conditions, variants of the 5-HTTLPR and STin2 VNTR polymorphisms of SERT have been shown to confer a heightened vulnerability to comorbid depression. OBJECTIVE: To determine whether the 5-HTTLPR, STin2 VNTR, and rs25531 polymorphisms of SERT are associated with poststroke depression (PSD) in stroke survivors. DESIGN: A case-control study in which stroke survivors were screened for depressive symptoms and assigned to either a depressed group or a nondepressed group. SETTING: Outpatient clinic. PARTICIPANTS: Seventy-five stroke survivors with PSD and 75 nondepressed stroke survivors. INTERVENTIONS: Blood or saliva samples were collected from each participant for DNA extraction and genotyping. MAIN OUTCOME MEASURES: The associations between the 5-HTTLPR, STin2 VNTR, and rs25531 polymorphisms and PSD. RESULTS: Individuals with the 5-HTTLPR s/s genotype had 3-fold higher odds of PSD compared with l/l or l/xl genotype carriers (odds ratio, 3.1; 95% confidence interval, 1.2-8.3). Participants with the STin2 9/12 or 12/12 genotype had 4-fold higher odds of PSD compared with STin2 10/10 genotype carriers (odds ratio, 4.1; 95% confidence interval, 1.2-13.6). An association of rs25531 with PSD was not shown. CONCLUSIONS: The 5-HTTLPR and the STin2 VNTR, but not the rs25531, polymorphisms of SERT are associated with PSD in stroke survivors. This gives further evidence of a role of SERT polymorphisms in mediating resilience to biopsychosocial stress.
Subject(s)
Depressive Disorder, Major/genetics , Depressive Disorder/genetics , Minisatellite Repeats/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Stroke/genetics , Adult , Aged , Alleles , Case-Control Studies , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Female , Gene Frequency/genetics , Genetic Carrier Screening , Genotype , Humans , Male , Middle Aged , Odds Ratio , Stroke/diagnosis , Stroke/psychologyABSTRACT
This study investigates the association of psychological symptoms with the distribution of two serotonin transporter gene (SERT) polymorphisms, located in the promoter region (5-HTTLPR) and in intron 2 (STin2 VNTR), in patients with irritable bowel syndrome (IBS). Participants, 21 men and 117 women, were assessed for mental health history and current psychological distress. A blood sample was used for genotyping. Participants who were homozygous for the short allele of 5-HTTLPR or carried a STin2.9 VNTR allele were significantly more likely to have a history of depression. Participants did not differ by genotype in their history of anxiety or suicidal ideation nor in their current levels of depression, anxiety, or general psychological distress. The results support a biopsychosocial model of IBS in which SERT genotype modifies the risk for depressive episodes. Long term, practitioners may individualize treatment of patients with IBS using genotype as one of the factors.
