Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy based on anthracyclines and ifosfamide for high-risk soft tissue sarcomas (STS) of the extremities and trunk is a controversial treatment option. There are substantial interindividual differences in clinical outcomes in patients treated with neoadjuvant chemotherapy. The aim of this study was to evaluate, as biomarkers, polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, or drug targets and their association with toxicity and survival in STS patients treated with neoadjuvant chemotherapy.

Genetic Variants as Predictors of Irinotecan-Induced Severe Gastrointestinal Toxicity in Metastatic Colorectal Cancer Patients.

Irinotecan is widely used in the treatment of metastatic colorectal cancer (mCRC) despite its severe toxicities. Toxicity is often associated with the genotype. An explanation for idiopathic toxicity beyond the biomarker, however, remains a major concern for clinicians.

Association study of polymorphisms within inflammatory genes and methylation status in treatment response in major depression.

Background: Although pharmacogenetics for major depressive disorder (MDD) is gaining momentum, the role of genetics in differences in response to antidepressant treatment is controversial, as they depend on multifactorial and polygenic phenotypes. Previous studies focused on the genes of the serotonergic system, leaving apart other pathological factors such as the inflammatory pathway. The main objective of the study was to assess whether treatment response might be associated with specific inflammation-related genetic variants or their methylation status.

Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients.

Background: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients.

Aim: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX.

Patients & Methods: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes.

An exploratory association study of the influence of noradrenergic genes and childhood trauma in Borderline Personality Disorder.

This study investigated the possible association of 40 polymorphisms within 4 noradrenergic genes with BPD risk and the modulating effect of childhood trauma on these associations in 481 BPD subjects and 442 controls. COMT rs5993882, DBH rs77905 and SLC6A2 rs1814270 showed associations with BPD, which were modulated by childhood trauma. However, none of these findings survived Bonferroni correction.

The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder.

Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis.

HIV-infection, atherosclerosis and the inflammatory pathway: candidate gene study in a Spanish HIV-infected population.

Background: Higher prevalence of atherosclerosis and higher cardiovascular risk is observed in HIV-infected individuals. The biological mechanisms underlying these processes are unclear. Several studies have implicated genetic variants in the inflammatory genes in cardiovascular disease and in HIV natural course infection.

Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder.

The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of stress responses. Increased methylation of the promoter region of the glucocorticoid receptor gene (NR3C1) has been described both in subjects with history of childhood trauma and in patients with Borderline Personality Disorder (BPD). However, no data on the possible association between a higher methylation of this gene and clinical severity is available.

Exploring the interaction between childhood maltreatment and temperamental traits on the severity of borderline personality disorder.

Background: Childhood maltreatment and temperamental traits play a role in the development of Borderline Personality Disorder (BPD). The aim of the present study was to assess the involvement and the interrelationship of both factors in the clinical severity of BPD.

Method: The self-reported history of childhood trauma, psychobiological temperamental traits, and severity of BPD symptoms were evaluated in 130 subjects with BPD.

Effect of FTO, SH2B1, LEP, and LEPR polymorphisms on weight gain associated with antipsychotic treatment.

Weight gain is one of the major adverse effects of antipsychotics. Although mechanisms remain unclear, genetic susceptibility has become increasingly attractive as a potential mechanism that could explain a significant part of interindividual variability. Most investigations have explored genes related with the mechanism of action of antipsychotic drugs.

Serotonin transporter polymorphisms and early response to antipsychotic treatment in first episode of psychosis.

There is substantial evidence suggesting that individual variability in antipsychotic treatment response could be genetically determined. Variations in several serotonin transporter (5-HTT) gene polymorphisms have been associated with antipsychotic response among chronic patients with schizophrenia, although their implication in early response among first-episode patients remains unclear. Two polymorphisms in the 5-HTT gene (a 44 bp insertion/deletion in the promoter region and the functional polymorphism rs25531) were genotyped in a sample of 147 drug-naïve patients experiencing a first episode of a non-affective psychosis.

Catechol-O-methyltransferase Val158Met polymorphism and clinical characteristics in first episode non-affective psychosis.

Catechol-O-methyltransferase (COMT) Val158Met polymorphism has been identified as a potential etiologic factor in schizophrenia. It has been proposed that this polymorphism could be associated with specific clinical markers. The aim of the study was to evaluate the influence of COMT Val158Met polymorphism genotype in the phenotypic expression of first episode psychosis at onset.

Association between the interleukin-1 receptor antagonist gene and negative symptom improvement during antipsychotic treatment.

The contribution of immune system to schizophrenia has been an important area of focus in schizophrenia research. Several genetic variants in the cytokine system have been associated with the pathogenesis of schizophrenia. The purpose of this study was to determine whether a pharmacogenetic relationship exists between a variable number of tandem repeats (VNTR) polymorphism in the interleukin-1 receptor antagonist gene (IL-1RN) and clinical improvement during antipsychotic treatment in patients with a first non-affective psychotic episode.

The -1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity.

Background: The -1438A/G single nucleotide polymorphism (SNP) lies just upstream of two alternative promoters for the 5-hydroxytryptamine type 2A (5-HT2A) receptor gene (HTR2A) and is in strong linkage disequilibrium with the 102T/C SNP. Both SNPs are associated with numerous psychiatric disorders and related phenotypes. A possible functional affect of the -1438A/G SNP might underlie associations of both linked SNPs with these neuropsychiatric disorders.