Exocytosis-related genes and response to methylphenidate treatment in adults with ADHD.

Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD. The sample comprised 433 subjects, of which 272 (62.8%) have completed the short-term IR-MPH treatment (at least 30 days). The main outcome measure was the categorical variable of short-term response to IR-MPH based on the Swanson, Nolan and Pelham Rating Scale version 4 (SNAP-IV), and on the clinical global impression-improvement scale. Additional analyses evaluated the percentage of SNAP-IV symptom reduction for each dimension as well as short- and long- (7 years) term treatment persistence. SYT1-rs2251214 was associated with the categorical short-term response to IR-MPH (P=0.006, PFDR=0.028), and with the percentage of inattention and oppositional defiant disorder symptoms reduction (P=0.007, PFDR=0.028 and P=0.017, PFDR=0.048, respectively). SYT1-rs2251214 was also associated with short-term treatment persistence (P=0.018, PFDR=0.048), and with months of treatment (P=0.002, PFDR=0.016) in the long-term protocol. Our findings suggest that SYT1-rs2251214 presents a broad influence in IR-MPH response variability in adults with ADHD, being involved with both symptom response and treatment persistence. If such findings are replicated, SytI could represent a key element in MPH pharmacodynamics in adults with ADHD.

The influence of the S19W SNP of the APOA5 gene on triglyceride levels in southern Brazil: interactions with the APOE gene, sex and menopause status.

BACKGROUND AND AIMS: Hypertriglyceridemia is an important independent risk factor for coronary artery diseases and is determined by a wide range of factors, both genetic and exogenous. The A5 apolipoprotein, which is associated with the synthesis and removal of triglycerides (TG), is encoded by the APOA5 gene. One of the polymorphisms of this gene that has been the focus of a large number of studies, and which appears to be associated with increased TG, is S19W (rs 3135506). In this study, we examined the influence of this single nucleotide polymorphism (SNP) on TG levels of a sample of southern Brazilians. METHODS AND RESULTS: Samples obtained from 567 people of European descent were genotyped; interactions between this variant and anthropometric variables were analyzed, and the effects of lifestyle, sex, menopause, and variations of the APOE gene were evaluated. We found that the 19W allele is associated with increased TG (p = 0.025) and that this influence was modulated by sex (p = 0.003), menopause (p = 0.022) and the presence of the E*4 allele (p = 0.027). CONCLUSION: Our data showed, for the first time, the importance and magnitude of the influence of the S19W variant in a southern Brazilian population.

Analytical reliability of four oral fluid point-of-collection testing devices for drug detection in drivers.

BACKGROUND: Point-of-collection testing (POCT) devices for psychoactive substance detection through oral fluid samples are used in several countries for traffic enforcement. However, the reported reliability of such devices is quite heterogeneous among studies, and evaluating and comparing their analytical performance is of paramount importance to guide enforcement policies. AIM: To evaluate the analytical reliability of four POCT devices for the detection of cocaine and cannabinoids using oral fluid samples of Brazilian drivers. METHOD: A total of 168 drivers were recruited during standard roadblockfI procedures in Southern Brazil. Subjects were screened using one of the following POCT devices: the DDS2™, the DOA MultiScreen™, the Dräger Drug Test 5000™ and the Multi-Drug Multi-Line Twist Screen Device™ (MDML). Results of the screening tests were compared with chromatographic analyses in order to obtain the reliability parameters. RESULTS: The prevalence of confirmed positive samples for cocaine and cannabinoids were 9 % and 4.4 %, respectively. For cocaine, three POCT devices (MDML™, Dräger DrugTest 5000™, DOA MultiScreen™) showed good reliability, greater than 80 % of performance measures, using guidelines for research on drugged driving published by Walsh et al. (cutoff 10ng/mL). However, for cannabinoids, the devices had low reliability-only Dräger DrugTest 5000™ had good performance using cut-offs proposed by Walsh et al. (cutoff 2ng/mL). CONCLUSION: We observed a high prevalence of drivers testing positive for cocaine and cannabinoids. Most devices achieved good reliability performance for cocaine detection using cutoffs proposed by Walsh et al. or using the device's own cutoff. Instead, the reliability for cannabinoid detection obtained the desired parameters in just one device using cut-offs proposed by Walsh et al. and its own cutoff. Difficulties in detecting cannabinoids at the roadside should be better evaluated before the implementation of such tests.