Related Experiment Video
Updated: Jul 12, 2026
10:39
3D-Neuronavigation In Vivo Through a Patient's Brain During a Spontaneous Migraine Headache
Published on: June 2, 2014
The wolframin His611Arg polymorphism influences medication overuse headache
C Di Lorenzo1, G Sances, G Di Lorenzo
1Department of Neurology and ORL, University Center for Adaptive Disorders and Headache (UCADH), University of Rome La Sapienza, Polo Pontino, Latina, Italy. cherub@inwind.it
Neuroscience Letters
|August 28, 2007
Summary
Wolframin (WFS1) gene variations are linked to increased medication overuse headache (MOH) drug consumption and depression. This WFS1 polymorphism may influence drug-seeking behavior in MOH patients.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Wolframin (WFS1) gene mutations cause Wolfram syndrome.
- WFS1 gene polymorphisms are associated with psychiatric disorders and substance dependence.
Purpose of the Study:
- To investigate the impact of WFS1 gene polymorphisms on medication overuse headache (MOH).
- To compare clinical features between different WFS1 genotypes in MOH patients.
Main Methods:
- Analysis of the WFS1 His611Arg polymorphism in 82 MOH patients.
- Comparison of monthly drug consumption and depressive symptoms (using the BDI questionnaire) between Arg/Arg (R/R) and non-R/R genotype groups.
- Multivariate regression analysis to identify predictors of drug consumption.
Main Results:
- Patients with the R/R genotype exhibited significantly higher monthly drug consumption (p=0.00075).
- R/R genotype individuals reported more severe depressive symptoms (p=0.003).
- WFS1 polymorphism was the sole significant predictor of drug consumption (adjusted R2=0.122).
Conclusions:
- The WFS1 gene plays a role in the clinical presentation of MOH.
- WFS1 may influence the propensity for drug use in MOH, potentially via mechanisms similar to other addictive behaviors.
Related Concept Videos
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:27Pharmacogenetics of Drug Metabolism: Overview
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
01:24Drug Toxicity: Risk factors
Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
01:27Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
01:30Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...