Evaluation of pentraxin-3 in familial Mediterranean fever patients during attack and attack-free periods.

INTRODUCTION: Pentraxin-3 (PTX-3) is a prototype of pentraxin proteins that have been shown to be involved in acute phase response. In this study, we aimed to investigate the relationship between PTX-3 levels and familial Mediterranean fever (FMF) disease, and to evaluate PTX-3 as a novel diagnostic marker of FMF. METHOD: Forty-three male patients diagnosed with FMF and 42 healthy individuals were included in the study. Patients with other inflammatory diseases and patients who used drugs having anti-inflammatory properties were excluded from the research. Blood samples were obtained during both attack and attack-free periods. RESULTS: Patient attack periods were confirmed by combining physical examination and elevation of acute phase reactants. Acute phase reactants were significantly higher in attack versus attack-free periods (p < 0.01), however PTX-3 levels were not significantly different between the two periods. Additionally, PTX-3 levels in FMF patients were higher than in controls in both attack (917.29 ± 725.29 vs 451.83 ± 291.95, p < 0.01) and attack-free periods (748.23 ± 487.53 vs 451.83 ± 291.95, p < 0.01). CONCLUSION: In this study, we showed that PTX-3 levels, in both FMF attack and attack-free periods, were significantly higher than in the control group. Finally, PTX-3 may be a promising biomarker for FMF diagnosis and may predict FMF attacks (Tab. 2, Fig. 2, Ref. 18).

Predictive factors of complications and 30-day mortality in patients undergoing percutaneous endoscopic gastrostomy: the utility of C-reactive protein to albumin ratio.

BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) is a procedure that provides long term enteral nutrition. To investigate the predictors of PEG-related complications and 30-day mortality rates and evaluate the indicators for deciding whether to recommend elective PEG insertions, we sought to determine the complications and early mortality rates of patients who underwent PEG. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive adult patients who had undergone PEG for the first time between October 2016 and January 2019. The predictors of complications and 30-day mortality were analyzed with receiver operating characteristic (ROC) and logistic regression analysis. RESULTS: This study included 309 patients. Patients were excluded from the study if they were < 18 years of age or there were missing data about them. Out of 253 patients, 33 (13%) had complications and 32 (12.6%) died within one month after PEG insertion. A higher C-reactive protein (CRP) to albumin ratio was the only independent factor predicting the complications (odds ratio (OR) : 3.17 ; 95% CI : 1.26-8.00 ; p = 0.014). The independent predictive factors for 30-day mortality after PEG placement included higher urea levels and higher CRP to albumin ratios (OR : 3.78 ; 95% CI : 1.41-10.17 ; p = 0.008) (OR : 6.67 ; 95% CI : 1.87- 23.75 ; p = 0.003). The only predictor for both complications and 30-day mortality was the CRP to albumin ratio. CONCLUSIONS: When appropriate, the PEG procedure can provide a safe and effective method for enteral feeding. The CRP to albumin ratio can be used to predict complications and early mortality after PEG insertion. Because PEG is elective, higher CRP to albumin ratios can be helpful in deciding to select patients for the procedure.

Hyperammonemic encephalopathy in a patient with primary hepatic neuroendocrine carcinoma.

A 53-year-old male patient was admitted to our hospital with abdominal pain in the right upper quadrant. There was no change in laboratory investigations other than a slight increase in serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT). Computed tomography (CT) of the abdomen showed multiple hepatic nodular lesions in the liver. Tru-cut biopsy of the lesions was reported as well-differentiated neuroendocrine carcinoma. The patient received sandostatin treatment. After a few days, the patient was hospitalized in the intensive care unit with disturbance of consciousness and clinical features suggestive of encephalopathy. Serum ammonia level was found highly elevated. After the treatment with L-ornithine-L-aspartate, a remarkable improvement in the level of patient's sensorium occurred as well as a reduction in serum ammonia level within a few days. Transarterial chemoembolization (TACE) was performed one week later. The patient's condition began to worsen along with increase in serum ammonia level and he died because of hyperammonemic encephalopathy. There are case reports of hyperammonemia with some malignancies such as multiple myeloma, plasma cell leukemia, and leiomyosarcoma, or in some patients who have received chemotherapy. This case may suggest an association between hyperammonemia and neuroendocrine tumors.

Effect of Helicobacter pylori infection and eradication therapy on interleukin-6 levels in patients with Familial Mediterranean Fever.

It is being questioned if Helicobacter pylori infection, which causes a chronic inflammatory response, can increase the frequency and severity of attacks in patients with Familial Mediterranean Fever (FMF) and if the impact of inflammatory response can be diminished by eradication of the infection. To evaluate if there is difference in interleukin (IL)-6 levels of H. pylori-positive and -negative patients both before and during FMF attacks; if there is a change in IL-6 levels following successful eradication treatment; and if MEFV gene mutations have an effect on IL-6 levels. IL-6 levels were evaluated in 47 FMF patients before and during FMF attacks. Genetic testing to determine M694V, M694I, E148Q, V726V, M680I mutations was also performed in all patients. IL-6 levels were also determined after successful eradication of the infection in H. pylori-positive patients. IL-6 levels were compared in H. pylori-positive and -negative patients, and before and after eradication treatment in patients who cleared the infection. Number of patients in tested mutation groups was not enough to compare IL-6 levels in these groups. Thirty-four patients (73.9%) were H. pylori-positive. Before FMF attack there was no statistically significant difference in IL-6 levels of H. pylori-positive and -negative groups. IL-6 levels were significantly higher in both groups during the attacks than before the attacks (p < 0.05). There was a statistically significant decline in IL-6 levels both before and during FMF attacks, following eradication therapy in patients who cleared the infection (p < 0.05). In patients with homozygous M694V mutation, IL-6 levels before and during the FMF attacks were not significantly different in H. pylori-positive and -negative groups, despite a much lower level found in H. pylori-negative group (p > 0.05). Comparisons were not performed in other mutation groups because of small number of patients in each group. C-reactive protein (CRP) and fibrinogen levels were not significantly different between the groups (p > 0.05). We believe that the observation of IL-6 levels are lower both before and during FMF attacks both in H. pylori-negative patients and in patients who cleared the infection after eradication therapy is very important in the determination of the role of eradication of H. pylori on decreasing the frequency and severity of FMF attacks. As for today, the correlation between H. pylori infection and FMF seems unlikely; however, studies evaluating the interaction of cytokines in both diseases and their relations and roles will be needed to reach better conclusions.

Co-existence of Helicobacter pylori infection in patients with Familial Mediterranean Fever (FMF) and the effect of Helicobacter pylori on the frequency and severity of FMF attacks.

BACKGROUND: The inflammatory reactions both in Familial Mediterranean Fever and in Helicobacter pylori infection have similarities. Whether there is interactions in case of co-existence of both diseases has not been evaluated. AIM.: To evaluate, if there is a significant relation between H. pylori infection and Familial Mediterranean Fever; if H. pylori has an effect on the frequency and severity of Familial Mediterranean Fever attacks; and if eradication treatment has any affects. METHODS: Thirty-two Familial Mediterranean Fever patients were tested for H. pylori infection. Acute phase responses were evaluated and attack frequency and severity were determined in both H. pylori-positive and H. pylori-negative groups. Same determinations were done after the eradication treatment in H. pylori-positive patients. Levels of acute phase determinants as well as frequency and severity of attacks were compared in H. pylori-positive and -negative groups. RESULTS: C-reactive protein, erythrocyte sedimentation rate, white blood count and fibrinogen levels were significantly (p<0.01) higher during the attacks than before the attacks in all patients. However, there was no difference between the groups. H. pylori-positive patients have a higher frequency and a longer duration of attacks when compared to H. pylori-negative patients before treatment (p<0.05). The frequency was also significantly lower and duration was shorter in patients whose infections were eradicated (p<0.05). CONCLUSION: H. pylori infection was not significantly frequent in our group of Familial Mediterranean Fever patients. H. pylori can decrease both the frequency and the duration of the attacks. Studies that will evaluate the relationship of H. pylori and MEFV gene along with the roles of yet unknown cytokines, which can presumably play a role in the pathogenesis of both diseases, are needed to reach better conclusions.

Is the remarkable contradiction between histology and 14C urea breath test in the detection of Helicobacter pylori due to false-negative histology or false-positive 14C urea breath test?

We assessed the diagnostic value of the 14C urea breath test (UBT) in the detection of Helicobacter pylori compared with histology and the rapid urease test (RUT). The study included 68 patients (22 men and 46 women) with dyspeptic symptoms. H. pylori status was evaluated by 14C UBT, RUT and histology. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were determined for 14C UBT and for RUT. Histology revealed dense yeast-like micro-organisms in the biopsy specimens in all patients with false-positive results by 14C UBT (n = 8), a significantly higher proportion than in patients with negative 14C UBT (five of 31). The low specificity of the H. pylori 14C UBT should not be neglected by accepting histology results as false-negative. Gastric mucosal colonization by yeast-like micro-organisms with urease activity can account for the high frequency of false-positive results for 14C UBT.

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders.

BACKGROUND: Some cases of Tourette's syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection. METHODS: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67). Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity. RESULTS: TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers. However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls. Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies. CONCLUSIONS: TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls. Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

No association between low- and high-activity catecholamine-methyl-transferase (COMT) and attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children.

Biochemical and genetic studies of attention deficit hyperactivity disorder (ADHD) suggest that regulation of catecholamine neurotransmission is a key factor in the aetiology of the disorder. In particular, it is postulated that an underactive dopamine system is associated with the disorder. In this study we have tested this hypothesis by screening a clinical sample of Turkish children with the combined subtype of ADHD with a functional variant of catecholamine-methyl-transferase (COMT) that codes for high- and low-activity variants of the enzyme. Using within-family tests of association and linkage in a sample of 72 children, we found no evidence for a genetic association or linkage. We conclude that altered regulation of catecholamines due to this polymorphism does not have a significant main effect on the risk for ADHD in this population. However, it remains feasible that more minor effects or interacting effects with other genes or environment exist.

Familial Mediterranean fever. A review of the disease and clinical and laboratory findings in 105 patients.

BACKGROUND: The diagnosis of familial Mediterranean fever still remains clinical, since no specific laboratory test exists, other than a molecular genetic test which is not widely available. AIM: To evaluate the clinical findings in 105 Turkish patients; to compare these findings with those in the literature; and to make a brief review of the disease. METHODS: A total of 105 familial Mediterranean fever patients were evaluated either retrospectively (for those diagnosed before 1997), or prospectively (for those after 1997). A diagnostic criteria set was used in addition to the clinical and laboratory findings that can be seen in familial Mediterranean fever, including the newly described manifestations. Previously selected clinical and laboratory parameters were observed for three consecutive days. RESULTS: Of our patients, 88.5% were of Turkish, 3.8% of Armenian and 7. 6% of Jewish origin. Family history was positive in 87 (82.8%) patients. Involved site was peritoneum in 97 (92%), joints in 45 (42.8%) and pleura in 19 (18%). Frequency of myalgia/arthralgia was 24.7%, and skin findings were observed in 16. 1% of patients. Splenomegaly, not related to amyloidosis, was present in 21 (20%) patients. Meningeal, retinal or ovarian/testicular involvement was not observed. CONCLUSION: Identification of familial Mediterranean fever gene has led to the application of a molecular genetic test for the diagnosis of Familial Mediterranean Fever. Until genetic methods become widely available, diagnosis will remain clinical. Thus, awareness of various clinical forms and of the correct usage of diagnostic criteria in various patient populations is important.

Budd-Chiari syndrome as a complication of Behçet's syndrome. A case report.

Budd-Chiari syndrome (BCS) is a very infrequent complication of Behçet's syndrome. The authors report a young, male patient with Behçet's syndrome presenting with BCS. He underwent emergency surgery for thrombectomy but unfortunately died during the operation.

A case of rapidly progressive pulmonary aneurysm as a rare complication of Behçet's syndrome--a case report.

One of the severe complications of Behçet's syndrome is pulmonary arterial involvement. The authors report a patient with Behçet's syndrome who had the complications of multiple pulmonary arterial aneurysms presenting with hemoptysis and right ventricular thrombus. He underwent emergency surgery because of failure of intensive immunotherapy and died 2 months after the surgery.

Does eradication of Helicobacter pylori reduce hypergastrinaemia during long term therapy with proton pump inhibitors?

OBJECTIVES: To evaluate the effect of Helicobacter pylori (Hp) eradication therapy on blood gastrin levels in long-term PPI users, since proton pump inhibitors (PPIs) and Helicobacter pylori (Hp) are major causes of hypergastrinaemia. DESIGN: A prospective study. SUBJECTS: Twenty seven Hp (+) patients enrolled in the study. Twenty were given eradication treatment (ET group), and the rest were given symptomatic treatment (ST group). Those who remained Hp (+) after eradication therapy were also added into the ST group. Lansoprazol 30 mg/day was given to both groups for three months thereafter. RESULTS: Fasting and non-fasting blood gastrin levels (FGL and NFGL) were measured initially and one month and four months after treatment. At the end of fourth month, FGL was significantly higher than both initial and first month level (p < 0.01) in the ST group. NFGL in this group did not change significantly (p > 0.05) after eradication therapy. In the ET group, FGL was significantly higher in the fourth month than the first month (p < 0.001) and than the initial level (p < 0.05). NFGL was higher, but not statistically in the fourth month than in the first month (p > 0.05) and significantly lower than the initial level (p < 0.05) in this group. CONCLUSION: We suggest that testing for Hp positivity and treating it if detected would be an appropriate approach to avoid hypergastrinaemia, especially in candidate patients for long term PPI treatment.

Are sensory phenomena present in Sydenham's Chorea? Evaluation of 13 cases.

Sydenham's Chorea (SC) is an early complication of rheumatic fever caused by group A beta-hemolytic streptococcal infection that manifests itself with adventitious choreatic movements and behavioral problems. Sensory phenomena are the premonitory sensory experiences that are described prior to tics. Tic disorders and SC share common underlying neurobiological substrates, yet sensory phenomena have not previously been examined in SC. We aimed to explore the presence of sensory phenomena associated with choreatic movements in children with SC. Thirteen SC patients are examined on measures of sensory phenomena using a semi-structured instrument. 10 out of 13 patients described sensory phenomena. Five of the SC patients described sensory phenomena as "between physical and mental". The patients described physical feelings of tension in joints, tingling and trembling sensations on skin. 69 % of them described movements as "completely involuntary". Sites of choreatic movements that were consistently preceded by sensory phenomena were upper and lower extremities, and trunk. Children may have difficulty in articulating sensory phenomena due to the subjective nature of premonitory feelings in SC. We recommend exploring the sensory experiences that might accompany the choreatic movements in children with SC.

Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children.

The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample.

Gallbladder and gastric motility in patients with idiopathic slow-transit constipation.

OBJECTIVE: Idiopathic slow-transit constipation (STC) has been suggested to be a pangastrointestinal motility disorder. We investigated scintigraphically whether motility in the gallbladder and stomach was impaired in slow-transit constipation. METHODS: Twenty-four patients with STC were studied. Colon transit time, gallbladder motility, and solid-phase gastric emptying were measured by scintigraphy. RESULTS: Gallbladder dysmotility was observed in 8 of 18 (44.4%) patients. Mean gallbladder ejection fraction was 41.6 +/- 13.6% (range, 16.3-67.0%). Gastric emptying was delayed in 9 of 18 (50%) patients. Mean solid-phase gastric half-emptying time was 75 minutes. STC may be associated with impaired function of other gastrointestinal organs. Approximately half of patients with STC presented gallbladder or gastric dysmotility. CONCLUSION: STC may not be a pure colonic abnormality; it may be a component of a pangastrointestinal tract motility disorder involving several organs.

CagA status in dyspeptic patients with and without peptic ulcer disease in Turkey: association with histopathologic findings.

BACKGROUND: CagA seropositivity is closely associated with that of vacuolating cytotoxin (VacA). Helicobacter pylori strains positive for both VacA and CagA were reported to be strongly associated with peptic ulcer disease. Different results reporting that cagA gene is not associated with more serious diseases, lowers the importance of CagA protein as a marker. In this study, CagA seropositivity is examined in Turkish peptic ulcer and nonulcer dyspepsia patients; histopathologic scores of CagA (+) and CagA (-) groups were compared. MATERIALS AND METHODS: Sixty consecutive patients (one gastric ulcer, 13 duodenal ulcer and 46 nonulcer dyspepsia) (mean age 40.9 +/- 14.7; 33 women, 27 men) with dyspeptic complaints who underwent upper gastrointestinal (GI) endoscopy were included. Biopsies from the antrum and corpus were used for histopathologic examination and for rapid urease test. H. pylori-negative patients comprised the control group. Histopathologic findings were graded using a previously described grading system (for inflammation, activity, atrophy, intestinal metaplasia and H. pylori, grades from 0 to 3 were used to quantify the findings). In H. pylori-positive patients, antibodies against CagA protein were determined using an ELISA METHOD: RESULTS: H. pylori was (+) in 46 patients. One duodenal ulcer and 13 nonulcer dyspepsia patients were negative for H. pylori. CagA positivity is significantly higher in peptic ulcer patients [12/12] than in nonulcer dyspepsia patients [25/33]. While inflammation, activity and atrophy scores were significantly higher in CagA positive patients, intestinal metaplasia and H. pylori load scores were not. Although the histopathologic scores in controls were lower than CagA (-) group, statistical significance was observed only in inflammation and intestinal metaplasia scores. CONCLUSION: Development of more prominent gastritis and severe atrophy in CagA (+) patients is an indicator of the importance of CagA rather than H. pylori load. Therefore, we suggest that nonulcer dyspepsia patients should also be tested for CagA status along with the tests for H. pylori status; and a positive CagA testing should be considered as an indication for eradication treatment. If CagA is negative, further assesment should be performed to decide whether or not to treat the patient.

The effect of Helicobacter pylori eradication on gastric juice and blood ammonia concentrations and on visual evoked potentials in cirrhotics.

BACKGROUND: The primary source of ammonia is the gut. Ammonia can also be generated by the urease activity of Helicobacter pylori in the gastric mucosa. The aim of this study was to investigate the effect of H. pylori eradication on blood and gastric juice ammonia levels and on visual evoked potential (VEP) recordings in cirrhotic patients. MATERIALS AND METHODS: Male patients with cirrhosis and H. pylori infection were prospectively evaluated. All patients were given triple regimen for eradication for 10 days. Gastroscopy together with gastric juice sampling for ammonia and mucosal sampling for H. pylori status was performed before and after therapy. Gastric juice and blood ammonia levels were measured and VEP recordings were obtained before and after treatment. RESULTS: Twenty-seven patients were included in the study. Patients with overt clinical hepatic encephalopathy were excluded from the study. Twenty-four out of twenty-seven patients became H. pylori-negative after the treatment. Ammonia measurements and VEP recordings were evaluated in the 24 patients in whom eradication was successful. A slight but statistically significant decrease in blood and a considerable decrease in gastric juice ammonia levels were observed after treatment [from 44.23 micromol/l to 41.6 micromol/l compared with 3234 micromol/l to 2709 micromol/l, respectively (p <.05)] in patients in whom H. pylori was eradicated. VEP recordings were abnormal in 14 out of 24 patients before the treatment. Only four of these 14 patients with abnormal recordings showed improvement. (p > .05). CONCLUSIONS: Helicobacter pylori eradication in cirrhotics decreases blood and gastric juice ammonia concentrations whereas it does not provide an improvement in VEP recordings.

Seropositivity against Helicobacter pylori CagA in Turkish gastric cancer patients.

BACKGROUND: Increased prevalence of CagA in gastric cancer has been reported; yet, other reports suggest that the cagA gene is not associated with gastric cancer. GOALS: To evaluate the frequency of CagA seropositivity in Turkish patients with gastric cancer. STUDY: Thirty-two patients with gastric adenocarcinoma and 46 patients with nonulcer dyspepsia were examined for Helicobacter pylori status and for antibodies against CagA. RESULTS: H. pylori was positive in 56.3% of patients and in 71.7% of controls. CagA was positive in all patients in the study group, regardless of H. pylori positivity, and in 56.5% of the control group. CagA positivity in H. pylori -positive patients was significantly more frequent in patients with gastric cancer than in those with nonulcer dyspepsia ( p < 0.001). As for H. pylori -negative patients in both groups, CagA positivity was also more frequent in gastric cancer patients ( p < 0.001). CONCLUSION: Testing for H. pylori antibodies without testing for antibodies against CagA will miss patients with either recent or previous infection, which may be a cause of missing the relationship between H. pylori and gastric cancer. The authors think that testing for CagA in patients with dyspepsia can reveal which patients should be followed up for the risk of developing gastric cancer.

Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples.

Molecular genetic studies in attention deficit hyperactivity disorder (ADHD) have focussed on candidate genes within the dopamine system, which is thought to be the main site of action of stimulant drugs, the primary pharmacological treatment of the disorder. Of particular interest are findings with the dopamine transporter gene (DAT1), since stimulant drugs interact directly with the transporter protein. To date, there have been eight published association studies of ADHD with a 480 base-pair allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the gene, five that support an association and three against. We have analysed the same VNTR marker in a dataset of UK Caucasian children and an independent dataset of Turkish Caucasian children with DSM-IV ADHD, using the transmission disequilibrium test (TDT). Results from the UK (chi(2) = 8.97, P = 0.001, OR = 1.95), but not the Turkish sample (chi(2) = 0.93, P = 0.34) support association and linkage between genetic variation at the DAT1 locus and ADHD. When considered alongside evidence from other published reports, there is only modest evidence for the association, consistent with a very small main effect for the 480-bp allele (chi(2) = 3.45, P = 0.06, OR = 1.15), however we find significant evidence of heterogeneity between the combined dataset (chi(2) = 22.64, df = 8, P = 0.004).