Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin.

BACKGROUND: Aspirin is associated with gastrointestinal side effects such as gastric ulcers, gastric bleeding and dyspepsia. High-dose effervescent calcium carbasalate (ECC), a buffered formulation of aspirin, is associated with reduced gastric toxicity compared with plain aspirin in healthy volunteers, but at lower cardiovascular doses no beneficial effects were observed. AIM: To compare the prevalence of self-reported gastrointestinal symptoms between low-dose plain aspirin and ECC. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Questions about demographics, gastrointestinal symptoms in general and specific symptoms, comorbidity, and medication use including bioequivalent doses of ECC (100 mg) and plain aspirin (80 mg) were stated. We investigated the prevalence of self-reported gastrointestinal symptoms on ECC compared with plain aspirin using univariate and multivariate logistic regression analyses. RESULTS: A total of 16,715 questionnaires (32 %) were returned and eligible for analysis. Of these, 911 (5 %) respondents reported the use of plain aspirin, 633 (4 %) ECC and 15,171 reported using neither form of aspirin (91 %). The prevalence of self-reported gastrointestinal symptoms in general was higher in respondents using ECC (27.5 %) compared with plain aspirin (26.3 %), but did not differ significantly with either univariate (OR 1.06, 95 %CI 0.84-1.33), or multivariate analysis (aOR 1.08, 95 %CI 0.83-1.41). Also, none of the specific types of symptoms differed between the two aspirin formulations. CONCLUSIONS: In this large cohort representative of the general Dutch population, low-dose ECC is not associated with a reduction in self-reported gastrointestinal symptoms compared with plain aspirin.

Gastrointestinal symptoms in NSAID users in an 'average risk population': results of a large population-based study in randomly selected Dutch inhabitants.

AIM: Non-steroidal anti-inflammatory drug (NSAID) use is widespread and associated with gastrointestinal symptoms and complications. The aims of this study were to assess (i) gastrointestinal symptoms in users of prescribed and over-the-counter (OTC) NSAIDs and (ii) proton pump inhibitor (PPI) co-prescription rates in NSAID users at increased risk for gastrointestinal complications. METHODS: Surveys were sent to a randomly selected sample of the adult Dutch general population in December 2008. Questions included demographics, gastrointestinal symptoms, medication use and comorbidity. Main outcome measure was presence of gastrointestinal symptoms. RESULTS: A total of 18,317 surveys were returned (response rate 35%), of which 16,758 surveys were eligible for analysis. Of these, 3233 participants (19%) reported NSAID use. NSAID users more frequently reported gastrointestinal symptoms than persons not using NSAIDs (33% vs. 24%, p < 0.01). Respondents who specified on prescription NSAID use (n = 683) were older, reported more comorbidity, and experienced more gastrointestinal symptoms (41%) compared with OTC users (n = 894, 33%, p < 0.01). This difference was not statistically significant after adjustment for confounders (0.99, 95% CI 0.71-1.37). In respondents with an increased gastrointestinal risk profile, PPI co-prescription rates were 51% for on prescription users and 25% for OTC users. CONCLUSIONS: Prevalence of gastrointestinal symptoms was high in both prescribed and OTC NSAID users, emphasising the side effects of both types of NSAIDs. PPI co-prescription rates in NSAID users at risk for gastrointestinal complication were low.

Patient adherence to prescribed medication instructions for dyspepsia: the DIAMOND-study.

BACKGROUND: Insight into patient adherence is needed to enable an effect evaluation of medication for dyspepsia. OBJECTIVES: Adherence was explored by investigating two adherence outcome measures (completeness and intake fidelity) using data from the DIAMOND-study. METHODS: The DIAMOND-study is a pragmatic RCT comparing a 'step-up' with a 'step-down' treatment strategy. In step 1 participants (n =653) were instructed to use five pills/day for maximally 30 days: an antacid 4dd plus a placebo 1dd ('step-up') or a proton pump inhibitor 1dd plus a placebo 4dd ('step-down'). If the complaints persisted, step 2 was started (H(2)-receptor antagonist 2dd), and subsequently step 3 (five pills/day, placebo and verum vice versa from step 1). Completeness was assessed by pill counts, intake fidelity by patient questionnaires measuring the degree to which patients adhered to specific instructions concerning timing, frequency, dose and way of intake. RESULTS: In step 1, patients used on average 3.9 pills/day (78% of the prescribed doses), in step 2, 1.7 pills/day (85%) and in step 3, 3.6 pills/day (72%). For the four times daily pills, half of the patients used less than 80% of the prescribed pills per day. This was one third of the patients for the twice daily pills and one quarter for the once daily pills. There were no completeness differences between active or placebo medication and no differences between the study arms. As regards intake fidelity, 70% of the patients made one or more errors in the medication intake. CONCLUSION: There is room for improvement in adherence rates for dyspepsia medication.

Catechol-O-methyltransferase (COMT) gene variants and pain in chronic pancreatitis.

BACKGROUND: Pain is the major symptom of chronic pancreatitis. The role of genetics in pancreatic pain is unclear. Catechol-O-methyltransferase (COMT) regulates enkephalin levels and influences pain perception. The COMT gene contains functional polymorphisms that have been found to influence human pain perception. The aim of our study was to investigate COMT single-nucleotide polymorphisms (SNP s) and diplotypes in chronic pancreatitis patients and healthy controls. METHODS: We genotyped four COMT gene SNP s: c.1-98A>G (rs6269), c.186C>T (p.=) (rs4633), c.408C>G (p.=) (rs4818) and c.472G>A (p.Val158Met) (rs4680) using a dual-colour discrimination assay in 240 chronic pancreatitis patients and 445 controls. We generated five diplotypes with a frequency >0.5% and compared prevalence between patients and controls. RESULTS: There was no significant association between the SNPs in the COMT gene and chronic pancreatitis. The diplotype ATCA÷ACCG was more prevalent in controls compared with patients (OR 0.48, 95% CI 0.24 to 0.93, p=0.03) where the most common diplotype GCGG ÷ATCA served as reference. However, after correction for multiple testing, this is not a significant difference. The distribution of other diplotypes was not significantly different between patients and controls. CONCLUSION: COMT SNP s and diplotypes are not associated with chronic pancreatitis. As a consequence, our results do not support a significant role for the COMT gene in chronic pancreatitis.

Adding familial risk assessment to faecal occult blood test can increase the effectiveness of population-based colorectal cancer screening.

BACKGROUND: The Dutch Health Council recently recommended the introduction of a colorectal cancer (CRC) screening programme by faecal occult blood testing (FOBT) for individuals aged 55-75 at population risk of CRC. Individuals at an increased familial CRC risk (≥ 2 times population risk) should be identified at a younger age, so they and their relatives can receive earlier, more intensive surveillance instead of FOBT. AIMS: To determine the percentage of participants with a positive FOBT in a CRC screening programme with an increased familial CRC risk. METHODS: In a population-based study, 10,569 individuals aged 50-75 received an FOBT. Individuals with a positive FOBT were invited for colonoscopy and familial risk assessment. Participants with an average familial CRC risk were compared to those with an increased risk. Increased familial CRC risk was defined as a cumulative lifetime risk of CRC of at least 10%. RESULTS: Of 6001 participants, 430 had a positive FOBT, of whom 324 (63% males; mean age 63 years) completed colonoscopy and familial risk assessment. CRC (n=22) and/or advanced adenomas (n=122) were found in 133 participants. Familial CRC risk was increased in 6% of participants with a positive FOBT. No significant differences were found between participants with an average versus an increased familial CRC risk. CONCLUSION: Six percent of participants with a positive FOBT had an increased familial CRC risk. Identifying at-risk participants enables them and their relatives to undergo regular colonoscopies. Adding familial risk assessment to FOBT screening may thus prevent a substantial number of CRCs.

[Nationwide colorectal cancer screening]. / Bevolkingsonderzoek naar darmkanker.

Usually, colorectal cancer presents with complaints in a late stage, but can be detected in an earlier stage, with better prognosis, by colonoscopy. Using colonoscopy, also precancerous tumours, adenomas, can be detected and excised, but only in a national screening programme. However primary screening with colonoscopy is too burdensome and expensive. Out of all the screening alternatives, only of the faecal occult blood tests (faeces tests) a decreased colorectal cancer mortality has been proven. It stands to reason that the new generation immunochemical faeces tests, can reduce colorectal cancer mortality more effectively, and these tests have, more than the alternatives, a good balance between efficiency, straightforwardness and costs. Recently, the Dutch National Health Council recommended to introduce nationwide colorectal cancer screening, using an immunochemical faecal occult blood test.

Cutoff value determines the performance of a semi-quantitative immunochemical faecal occult blood test in a colorectal cancer screening programme.

BACKGROUND: The cutoff of semi-quantitative immunochemical faecal occult blood tests (iFOBTs) influences colonoscopy referrals and detection rates. We studied the performance of an iFOBT (OC-Sensor) in colorectal cancer (CRC) screening at different cutoffs. METHODS: Dutch screening participants, 50-75 years of age, with average CRC risk and an iFOBT value >or=50 ng ml(-1) were offered colonoscopy. The detection rate was the percentage of participants with CRC or advanced adenomas (>or=10 mm, >or=20% villous, high-grade dysplasia). The number needed to scope (NNTScope) was the number of colonoscopies to be carried out to find one person with CRC or advanced adenomas. RESULTS: iFOBT values >or=50 ng ml(-1) were detected in 526 of 6157 participants (8.5%) and 428 (81%) underwent colonoscopy. The detection rate for advanced lesions (28 CRC and 161 with advanced adenomas) was 3.1% (95% confidence interval: 2.6-3.5%) and the NNTScope was 2.3. At 75 ng ml(-1), the detection rate was 2.7%, the NNTScope was 2.0 and the CRC miss rate compared with 50 ng ml(-1) was <5% (N=1). At 100 ng ml(-1), the detection rate was 2.4% and the NNTScope was <2. Compared with 50 ng ml(-1), up to 200 ng ml(-1) CRC miss rates remained at 16% (N=4). CONCLUSIONS: Cutoffs below the standard 100 ng ml(-1) resulted in not only higher detection rates of advanced lesions but also more colonoscopies. With sufficient capacity, 75 ng ml(-1) might be advised; if not, up to 200 ng ml(-1) CRC miss rates are acceptable compared with the decrease in performed colonoscopies.

Earlier stages of colorectal cancer detected with immunochemical faecal occult blood tests.

BACKGROUND: The aim of colorectal cancer screening is to improve prognosis by the detection of early cancer and precursor stages. We compared the stage distribution of asymptomatic colorectal cancer patients detected by a positive immunochemical or guaiac-based faecal occult blood test (FOBT) with symptomatic colorectal cancer patients. METHODS: In a longitudinal cohort study tumour stages were assessed in 144 symptomatic (mean age 69.3 years, 56% male) and 41 asymptomatic colorectal cancer patients (mean age 64.9 years, 56% male) of which 11 were detected with guaiac FOBT s (G-FOBT, Hemoccult-II) and 30 with immunochemical FOBTs (I-FOBT, OCSensor). Stage distributions were used to calculate average stage specific predicted five-year survival rates and to analyse group differences with Wilcoxon log-rank test. RESULTS: Colorectal cancer was detected in significantly earlier stages in symptomatic compared with asymptomatic patients patients (p<0.0001). Average stage specific predicted five-year survival was 59.1% in symptomatic and 76.6% in asymptomatic patients. Compared with the symptomatic patients the stage distribution for colorectal cancer patients detected with Hemoccult-II was not significantly different(p=0.29), whereas colorectal cancer was detected at significantly earlier stages with the OCSensor (p<0.0001).Treatment could be confined to colonoscopy in 27% of the asymptomatic patients compared with 3% of the symptomatic patients (p<0.0001). Cancer distribution over the colon was comparable between symptomatic and asymptomatic patients (p=0.3). CONCLUSIONS: Compared with symptomatic patients,patients detected by FOBT and especially immunochemical FOBT , presented significantly more often at earlier stages suggesting increased survival. Additionally treatment could more often be confined to colonoscopy.

Serum bactericidal activity against Helicobacter pylori in patients with hypogammaglobulinaemia.

The two major primary antibody deficiency disorders are X-linked hypogammaglobulinaemia (XLA) and common variable immunodeficiency (CVID). CVID patients have an elevated risk for gastric cancer and extra-nodal marginal zone lymphoma. Both diseases are associated with Helicobacter pylori infection. We investigated whether antibody deficiency leads to defective serum bactericidal activity against H. pylori. We also investigated the correlation with immunoglobulin (Ig)M levels and observed the terminal complement complex (TCC) activity. Sera of 13 CVID patients (four H. pylori positive), one patient with hyper-IgM syndrome, one patient with Good syndrome (both H. pylori positive), five XLA patients, four H. pylori seropositive controls, four H. pylori seronegative controls and a sample of pooled human serum (PHS) were incubated in vitro with bacterial suspensions of H. pylori for 30 min. After 72 h of culture, colony-forming units were counted. TCC formation was measured by enzyme-linked immunosorbent assay. We found that normal human serum is bactericidal for H. pylori, whereas heat-inactivated serum shows hardly any killing of H. pylori. Serum (1%) of hypogammaglobulinaemia patients has a decreased bactericidal activity against H. pylori. Helicobacter pylori-positive (HP(+)) normal individuals show more than 90% killing of H. pylori, whereas CVID patients show 35% killing (P = 0.007) and XLA patients only 19% (P = 0.003). Serum (1%) of HP(+) volunteers showed significantly better killing compared with serum of H. pylori-negative (HP(-)) volunteers (P = 0.034). No correlation between (substituted) IgG levels and serum bactericidal activity was found, but a weak correlation between total serum IgM and serum bactericidal activity was found. In conclusion, serum bactericidal activity against H. pylori is decreased in patients with hypogammaglobulinaemia. Heat treatment of the serum abolished the bactericidal capacity, indicating that complement activity is essential for the bactericidal effect.

Influence of gastric mucosal status on success of stepwise acid suppressive therapy for dyspepsia.

BACKGROUND: The most effective initial treatment strategy of dyspepsia is still under debate. Individual biological characteristics, such as condition of gastric mucosa, might contribute to selection of the most appropriate acid suppression treatment strategy. AIM: To assess whether pre-treatment testing of gastric mucosal status is relevant for treatment success in an RCT comparing step-up and step-down therapies in newly diagnosed dyspepsia patients. METHODS: Baseline serum samples were collected to assess gastric mucosal status using serum levels of pepsinogens-I&II, gastrin-17, and Helicobacter pylori IgA/IgG-antibodies. The 6-month treatment success was compared between step-up and step-down for patients with serum diagnoses: normal; gastritis; corpus atrophy or antrum atrophy. RESULTS: In all, 519 patients (M/F: 249/270, age: 47 (18-85) years, 29%H. pylori+) were randomized to step-up (n = 293) or step-down (n = 226). Normal mucosa, gastritis and corpus atrophy were diagnosed serologically in 70%, 28% and 2% of the patients, evenly distributed between the strategies (P = 0.65). Treatment success was achieved in respectively, 69%, 70% and 70% for the serum diagnosis groups, and did not differ between the strategies. CONCLUSIONS: Dyspepsia treatment success could not be predicted by gastric mucosal status. Therefore, serum diagnosis of gastric mucosal status is no useful tool for patient allocation to acid suppressive treatment strategies.

Psychopathology is associated with dyspeptic symptom severity in primary care patients with a new episode of dyspepsia.

BACKGROUND: Personality and psychiatric disorders are reported to be more common in dyspeptic patients with severe complaints, but it remains unclear whether this association exists for patients with mild and moderate dyspepsia. AIM: To study the association between dyspeptic symptom severity and psychopathology, major life events and coping ability in patients with a new episode of dyspepsia. METHODS; Dyspeptic symptom severity was measured using the validated eight symptom Veldhuyzen van Zanten questionnaire. Psychopathology was measured using the Symptom Check List-90 (SCL 90). Major life events were measured with a modified version of the Social Readjustment Rating Scale (SRRS). Coping styles were measured by a short version of the Utrecht Coping Questionnaire, distinguishing six coping styles. Linear regression was used to assess the relationship between dyspepsia symptom severity and psychological factors. RESULTS: In all, 664 patients with a new episode of uninvestigated dyspepsia, aged >18 years were included. Dyspeptic symptom severity was positively correlated with the presence of depression (P < 0.01), somatization symptoms (P < 0.01), use of an active coping style (P < 0.01) and negatively correlated with age (P < 0.01). CONCLUSIONS: Primary care patients consulting with dyspepsia have higher levels of depression and somatization especially at younger age. An active coping style is associated with dyspepsia symptom severity.

Getting adequate information across to colorectal cancer screening subjects can be difficult.

OBJECTIVES: Participation in screening should be the outcome of an informed decision. We evaluated whether invitees in the first Dutch colorectal cancer (CRC) screening programme were adequately informed after having received a detailed information leaflet. METHODS: A total of 20,623 subjects aged 50-75 years were invited to the fecal occult blood test (FOBT) screening programme. All received a detailed information leaflet by mail between May 2006 and January 2007. After two weeks, a reminder letter was sent to all invitees, accompanied by a survey on CRC and screening. RESULTS: The survey was completed by 9594 invitees (47%). Almost all responders (99%) found the leaflet clear and readable. Almost all indicated that CRC can be treated better if found early (99%). Only 20% of the responders answered all knowledge-related answers correctly. Almost half of the responders (47%) believed that a negative FOBT excludes the presence of CRC. Older age and having a positive family member for CRC were correctly identified as risk factors by 80%. CONCLUSION: This study demonstrates that although an information leaflet was reported as being clear and readable, the information provided in it was not always understood well. This suggests that other educational options should be investigated in order to improve general knowledge of CRC in screening invitees.

Low priority main reason not to participate in a colorectal cancer screening program with a faecal occult blood test.

BACKGROUND: Compared with screening programs for breast and cervical cancer, reported participation rates for colorectal cancer (CRC) screening are low. The effectiveness of a screening program is strongly influenced by the participation rate. The aim of this study was to investigate the main reasons not to participate in a population-based, invitational CRC screening program. METHODS: In the Dutch study program for CRC screening, a random selection of 20 623 persons were invited received a faecal occult blood test. Of the non-participants, 500 were randomly selected and contacted for a standardized telephone interview from November 2006 to May 2007 to document the main reason not to participate. RESULTS: In total, 312 (62%) non-participants could be included for analysis. Most frequently, reported reasons for non-participation were time-related or priority-related (36%), including 'did not notice test in mailbox' (13%) and 'forgot' (8%). Other reasons were health-related issues, such as 'severe illness' (9%), or emotional reasons, such as 'family circumstances' (7%). CONCLUSIONS: The majority of the reported reasons not to participate reflect low priority for screening. Adding extra instructions and information, and addressing specific concerns through additional interventions should be considered to improve individual decision-making about participation in future CRC population-based screening programs.

[Screening for colorectal cancer: definitely implement]. / Screening op dikkedarmkanker: zeker invoeren.

An individual's lifetime risk of developing colorectal cancer is estimated at 5%. Currently, screening the asymptomatic population is the only way to effectively reduce mortality. Colorectal cancer screening meets prospectively defined scientific criteria for screening and is more cost-effective than existing screening programmes for cancers of the cervix and breast. Therefore, screening for colorectal cancer should be implemented.

Gastrointestinal symptoms are still common in a general Western population.

BACKGROUND: Results from studies conducted in the late 1980s and early 1990 s showed that gastrointestinal symptoms were common among the general population. Meanwhile, lifestyle habits have changed and important treatment options have been introduced. This might have influenced symptom prevalence. METHODS: This study aimed to describe the current prevalence of upper and lower gastrointestinal symptoms within the general population. For this purpose, a demographically representative sample of the Dutch population within the city of Nijmegen and surrounding areas was selected after careful comparison with demographic figures from a government demographic database. Participants were invited to fill in a valid self-report questionnaire about gastrointestinal symptoms and prevalence figures were calculated. RESULTS: A total of 5000 questionnaires was sent and 1616 (32%) were returned. Of these, 839 (52%) subjects reported having had upper (43%) or lower (38%) gastrointestinal symptoms in the past four weeks. The most prevalent individual symptoms reported were flatulence (47%), abdominal rumbling (40%), bloating (37%), alternating solid and loose stools (31%), belching (25%) and postprandial fullness (25%). People who smoked or used a proton pump inhibitor had an increased risk for reporting upper as well as lower gastrointestinal symptoms (OR 1.99; 95% CI 1.56 to 2.55, and OR 1.37; 95% CI 1.01 to 1.75, respectively for smoking; and OR 3.17; 95% CI 2.17 to 4.72, and OR 2.14; 95% CI 1.49 to 3.08, respectively for PPIs). CONCLUSION: Both upper and lower gastrointestinal symptoms are very common in a representative sample of a general Western population.

UGT1A7 polymorphisms in chronic pancreatitis: an example of genotyping pitfalls.

UDP-glucuronosyltransferases (UGT) catalyze the glucuronidation of various compounds and thus inactivate toxic substrates. Genetic variations reducing the activity of UGT1A7 have been associated with various gastrointestinal cancers. Most recently, the UGT1A7*3 allele has been reported as a significant risk factor for pancreatic disorders, but we could not confirm these data. This study focused on the possible causes for the noted discrepancy. UGT1A7 genotypes were assessed in 37 samples, which were previously analyzed for UGT1A7 polymorphisms by others. We determined genotypes by melting curve analysis and by DNA sequencing. Additionally, we produced UGT1A7*1 and *3 constructs with or without a mutation at position - 57 of UGT1A7 and analyzed various combinations of these constructs. In 14/37 samples UGT1A7 genotyping results differed. The discrepancy could be explained by polymerase chain reaction bias owing to an unbalanced allelic amplification which was caused by a -57T>G variant located within the sequence of the chosen primer template in previous studies. Our findings indicate that most of the previously reported genetic associations between UGT1A7 and gastrointestinal cancers are based on primer-dependent genotyping errors.

The predictive value of vitamin B12 concentrations and hyperhomocysteinaemia for cardiovascular disease.

BACKGROUND: Cardiovascular disease has been associated with both homocysteine and vitamin B12 levels. However, little information is available about the mutual relation in cardiovascular patients. The aim of this study was to assess the prevalence of vitamin B12 deficiency in patients with cardiovascular disease, and to study the correlation with homocysteine levels. METHODS: Blood samples were taken from 229 patients who had been admitted to the Coronary Care Unit of the Heart-Lung Centre of the Radboud University Medical Centre in Nijmegen, the Netherlands. Patient demographics and clinical characteristics were assessed from medical files. Adjusted logistic regression was used to study the associations between vitamin B12, homocysteine and ischaemic heart disease. RESULTS: In 70 patients (33%) serum vitamin B12 levels were below the lower limit of normal (<203 ng/l). Sixty-nine patients (33%) had vitamin B12 concentrations in the lower normal range (between 203 and 339 ng/l). Plasma homocysteine levels above the upper limit of normal were found in 83 out of the 229 patients (36%). Adjusted odds ratios for both vitamin B12 (0.76, 95% CI 0.44-1.30) and homocysteine (1.27, 95% CI 0.74-2.18) levels did not show a statistical association with ischaemic heart disease. No association was found between serum vitamin B12 levels and plasma homocysteine. CONCLUSION: Our data suggest that hyperhomocysteinaemia and low serum vitamin B12 concentrations are independent and cannot be used as a diagnostic tool for ischaemic heart disease. (Neth Heart J 2007;15:291-4.).

Maintenance treatment with budesonide 6 mg versus 9 mg once daily in patients with Crohn's disease in remission.

BACKGROUND: In previous trials, budesonide 6 mg/day was able to prolong the time to relapse in patients with quiescent Crohn's disease and budesonide 9 mg/day was effective in active disease with limited side effects. The aim of this study was to compare the effectiveness of budesonide 9 mg vs 6 mg once daily on the maintenance of remission and occurrence of adverse events. METHODS: Double-blind, randomised trial in patients with Crohn's disease in remission. Patients were randomised to receive 6 mg/day or 9 mg/day of budesonide (Budenofalk) without concomitant treatment for Crohn's disease. Endpoints were the time to relapse and relapse rates after one year. RESULTS: Seventy-six patients were randomised to 6 mg/day and 81 patients to 9 mg/day. Survival analysis showed no differences in the time to relapse. One-year relapse rates were not significantly different (6 mg group 24%; 9 mg group 19%). Any adverse event was reported in 61 and 68% of patients in the 6 mg and 9 mg groups, respectively; none of the 12 serious adverse events were drug related. CONCLUSION: The one-year relapse rates were low and not significantly different between the group of patients treated with budesonide 6 mg vs 9 mg/day. Also, time to relapse and the number of adverse events were similar in both treatment groups.

Meta-analysis: a functional polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel syndrome.

BACKGROUND: Serotonin is associated with symptoms of the irritable bowel syndrome, its action is terminated by the serotonin transporter protein. AIM: To assess the association between a functional polymorphism in the gene encoding for activity of the serotonin transporter protein and the irritable bowel syndrome. METHODS: Meta-analysis of studies identified through a Medline, PubMed and Web of Science search, describing the prevalence of a polymorphism in the serotonin transporter gene creating long and short alleles. RESULTS: Eight eligible studies described a total of 1034 patients with the irritable bowel syndrome, and 1377 healthy controls. Presence of the short allele is not associated with an increased risk for the irritable bowel syndrome: OR 1.0; 95% CI: 0.7-1.4 for homozygous subjects, and OR 1.0; 95% CI: 0.8-1.2 for homozygous subjects and heterozygotes together. Although Caucasians and Asians had diverging genotypic frequencies, no association with the shot allele and irritable bowel syndrome was observed in subgroups: Asians OR 1.2; 95% CI: 0.9-1.6 and OR 1.1; 95% CI: 0.2-5.9; Caucasians OR 0.9; 95% CI: 0.5-1.7 and OR 0.9; 95% CI: 0.7-1.2, respectively, for homozygous subjects alone and for homozygous subjects and heterozygotes together. CONCLUSION: A genetic polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel.