ABCB1 gene polymorphisms are associated with suicide in forensic autopsies
Samuel Boiso Moreno1, Anna-Lena Zackrisson, Ingrid Jakobsen Falk
1Department of Medical and Health Sciences, Division of Drug Research, Clinical Pharmacology, Faculty of Health Sciences, Linköping University, Linköping, Sweden. samuel.boiso@gmail.com
Pharmacogenetics and Genomics
|July 4, 2013
Summary
Genetic variations in ABCB1 (P-glycoprotein transporter) may increase suicide risk. This study found specific ABCB1 polymorphisms were more common in individuals who died by suicide, suggesting a potential link.
Area of Science:
- Pharmacogenetics
- Forensic Toxicology
- Genetics
Background:
- ABCB1 gene polymorphisms influence P-glycoprotein function and drug response.
- Altered P-glycoprotein activity may affect central nervous system drug efficacy, including antidepressants and antipsychotics.
Purpose of the Study:
- To investigate the association between specific ABCB1 gene polymorphisms (1199G>A, 1236C>T, 2677G>T/A, 3435C>T) and completed suicide.
- To determine if these genetic variations are risk factors for suicide mortality.
Main Methods:
- Analysis of 998 consecutive Swedish forensic autopsies (individuals aged 18+).
- Genotyping of ABCB1 polymorphisms using pyrosequencing.
- Data collection from forensic pathology and toxicology databases for cause and manner of death.
Main Results:
- A significantly higher frequency of the T allele at ABCB1 positions 1236, 2677, and 3435 was observed in suicide cases compared to non-suicide cases.
- These findings indicate a potential genetic predisposition associated with suicide risk.
Conclusions:
- ABCB1 polymorphisms are associated with an increased risk of completed suicide in the studied forensic population.
- Further research is needed to elucidate the underlying biological mechanisms and clinical implications of these genetic associations.
Related Concept Videos
01:28Human Genetics
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
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...
01:16Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
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...
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...