Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus

<p>Abstract</p> <p>Background</p> <p><it>MCF2L2, ADIPOQ </it>and <it>SOX2 </it>genes are located in chromosome 3q26-27, which is linked to diabetic nephropathy (DN). <it>ADIPOQ </it>and <it>SOX2 </it>genetic polymorphisms are found to be associated with DN. In the present study, we first investigated the association between <it>MCF2L2 </it>and DN, and then evaluated effects of these three genes on the development of DN.</p> <p>Methods</p> <p>A total of 1177 type 1 diabetes patients with and without DN from the GoKinD study were genotyped with TaqMan allelic discrimination. All subjects were of European descent.</p> <p>Results</p> <p>Leu359Ile T/G variant in the <it>MCF2L2 </it>gene was found to be associated with DN in female subjects (P = 0.017, OR = 0.701, 95%CI 0.524-0.938) but not in males. The GG genotype carriers among female patients with DN had tendency decreased creatinine and cystatin levels compared to the carriers with either TT or TG genotypes. This polymorphism <it>MCF2L2-</it>rs7639705 together with SNPs of <it>ADIPOQ</it>-rs266729 and <it>SOX2</it>-rs11915160 had combined effects on decreased risk of DN in females (P = 0.001).</p> <p>Conclusion</p> <p>The present study provides evidence that <it>MCF2L2</it>, <it>ADIPOQ </it>and <it>SOX2 </it>genetic polymorphisms have effects on the resistance of DN in female T1D patients, and suggests that the linkage with DN in chromosome 3q may be explained by the cumulated genetic effects.</p

Caso raro de pneumotórax: adamantinoma metastático A rare case of pneumothorax: metastatic adamantinoma

Descrevem-se dois casos de metástases pulmonares de adamantinoma de ossos longos, o qual é uma neoplasia óssea de baixo grau que raramente metastatiza. Nos dois casos a apresentação clínica das metástases se deu por pneumotórax espontâneo secundário a escavação tumoral, fenômeno descrito em apenas três dos trabalhos consultados na literatura. São descritos os achados clínicos, radiológicos e anatomopatológicos, bem como os procedimentos adotados nos dois casos.<br>Here, we describe two cases of lung metastasis of adamantinoma of long bones, a low-grade bone neoplasm that rarely metastasizes. In both cases, the clinical presentation of the metastases was characterized by spontaneous pneumothorax secondary to tumor cavitation, a phenomenon described in only three of the studies reviewed in the literature. Clinical, radiological, and anatomopathological findings, as well as the procedures adopted in the two cases, are described

Common disorders are quantitative traits

After drifting apart for 100 years, the two worlds of genetics - quantitative genetics and molecular genetics - are finally coming together in genome-wide association (GWA) research, which shows that the heritability of complex traits and common disorders is due to multiple genes of small effect size. We highlight a polygenic framework, supported by recent GWA research, in which qualitative disorders can be interpreted simply as being the extremes of quantitative dimensions. Research that focuses on quantitative traits - including the low and high ends of normal distributions - could have far-reaching implications for the diagnosis, treatment and prevention of the problematic extremes of these traits