Genetic diagnostics of functional variants of the human dopamine D2 receptor gene.

Introduction: The importance of dopamine D2 receptors (DRD2) for central nervous dopaminergic signalling makes variants in the DRD2 gene potential modulators of the risk or course of various behavioural, psychiatric or neurologic diseases (e.g. addiction, schizophrenia, Parkinson's disease).

Functional variants of the human 5-lipoxygenase gene and their genetic diagnosis.

Variants in the 5-lipoxygenase (ALOX5) gene are first-line candidate causes for interindividual differences in diseases where leukotrienes play a key role, e.g., inflammatory and immune diseases, atherosclerosis, asthma or the acute respiratory distress syndrome (ARDS).

Pyrosequencing of polymorphisms in the COX-2 gene (PTGS2) with reported clinical relevance.

Introduction: Genetic variants in the prostaglandin-endoperoxide synthase 2 (PTGS2) gene, which codes for COX-2, have been identified to modulate the response to COX-2-inhibiting drugs and to be possible risk factors for the incidence or prognosis of cardiovascular or neoplastic diseases, Alzheimer's disease, multiple sclerosis, asthma or osteoarthritis. Clinical evidence thus suggests a clinical importance of COX-2 genetics reaching from disease risk or prognostics up to a personalized therapy with COX-2 inhibitors. The aim of this study was to develop rapid and reliable screening assays for PTGS2 mutations with reported clinical consequences.

Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms.

Background: A haplotype in the GTP cyclohydrolase 1 (dopa-responsive dystonia) gene (GCH1) is associated with decreased persistent pain. The aim of the present study was to develop a screening method for the pain-protective haplotype.

Methods: Complete genetic information for all 15 GCH1 DNA positions constituting the pain-protective GCH1 haplotype was available from 278 patients.

Pyrosequencing-based screening for genetic polymorphisms in cytochrome P450 2B6 of potential clinical relevance.

Objectives: Three exonic single nucleotide polymorphisms (SNPs) in the cytochrome P450 2B6 (CYP2B6) gene, 516G>T, 785A>G and 1459C>T, have been described to be associated with functional changes in the CYP2B6 catalytic activity or protein expression. They are therefore of potential clinical importance for drug efficacy and safety of CYP2B6 substrates, in particular of antiretroviral therapy regimes that include efavirenz. Therefore, we aimed at providing genetic screening assays for these three SNPs.

Rapid identification of three functionally relevant polymorphisms in the OATP1B1 transporter gene using Pyrosequencing.

Introduction: Clinical evidence suggests there are three single nucleotide polymorphisms (SNPs) of the solute carrier organic anion transporter family member B1 (SLCO1B1) gene for which in vivo evidence for a functional relevance for organic anion transporter polypeptides subgroup C (OATP1B1, formerly OATP-C) has been provided. These genetic variants have been shown to lead to altered pharmacokinetics of OATP1B1 substrates, mainly pravastatin, but also the irinotecan metabolite SN-38, estrone-3-sulfate, and estradiol-17beta-glucuronide. The authors therefore developed reliable and quick screening assays to identify the SLCO1B1 SNPs -11187G>A, 388A>G and 521T>C, in order to facilitate the judgment of their clinical role and to identify allelic frequencies of SNPs and haplotypes in a Caucasian random sample.

Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing.

Objective: To develop a rapid and reliable screening method for identifying the relevant cytochrome P450 (CYP) 1A2 alleles CYP1A2*1D (-2467Tdel), *1F (-163A>C), and *1K (-739T>G, -729C>T, -163A>C) that are in linkage disequilibrium with the functionally relevant CYP1A2 polymorphisms and therefore are considered to be predictive for the CYP1A2 phenotype.

Methods: CYP1A2 single nucleotide polymorphisms (SNPs) -2467Tdel, -739T>G, -729C>T, and -163A>C were screened for in 495 healthy Caucasian volunteers using newly developed pyrosequencing duplex and simplex assays. Conventional sequencing of randomly selected samples served as quality control.