Association between ABCB1 Polymorphisms and Ischemic Stroke in Korean Population
Young-Ock Kim1, Seung-Yu Kim, Dong Hwan Yun
1Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, Rural Development Administration, Eumseong 369-873, Korea.
Experimental Neurobiology
|January 16, 2013
Summary
Genetic variations in the ABCB1 gene are linked to ischemic stroke (IS) development and clinical features in the Korean population. Specifically, the rs3842 SNP shows associations with IS risk, hypertension, diabetes, and stroke severity.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Neuronal expression of ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) is observed following brain ischemia.
- Investigating the role of ABCB1 gene polymorphisms in ischemic stroke (IS) is crucial for understanding disease mechanisms and risk factors.
Purpose of the Study:
- To examine the association between ABCB1 gene single nucleotide polymorphisms (SNPs) and the development, risk factors, severity, and sequelae of ischemic stroke (IS).
- To analyze four specific ABCB1 SNPs: rs4148727, rs3213619, rs1128503, and rs3842 in relation to IS and its clinical phenotypes.
Main Methods:
- Genotyping of four ABCB1 SNPs (rs4148727, rs3213619, rs1128503, rs3842) in 121 IS patients and 291 control subjects.
- Statistical analysis using SNPStats and SPSS 18.0, including logistic regression models (codominant, dominant, recessive, log-additive) to evaluate genetic associations.
- Assessment of associations with IS development, hypertension, dyslipidemia, diabetes mellitus, National Institutes of Health Stroke Scale (NIHSS), and Modified Barthel Index (MBI).
Main Results:
- The rs3842 SNP showed a weak association with IS development.
- ABCB1 polymorphisms were nominally associated with hypertension (rs3213619, rs3842), dyslipidemia (rs1128503), diabetes (rs3842), and stroke severity (NIHSS, rs4148727).
- A strong association was found between the rs3842 SNP and IS with hypertension, particularly in the recessive model.
Conclusions:
- The ABCB1 gene, particularly the rs3842 polymorphism, may play a role in the development and clinical presentation of ischemic stroke in the Korean population.
- These findings highlight the potential of ABCB1 gene variations as biomarkers for IS risk and clinical phenotypes, warranting further investigation.
Related Concept Videos
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...
01:29Pharmacogenetic 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...
01:15Ischemic Stroke l: Introduction
Ischemic stroke is an acute cerebrovascular condition in which blood flow to a brain region is suddenly interrupted, leading to tissue infarction. Neurons depend on continuous oxygen and glucose supply, so even brief reductions in perfusion cause energy failure, ionic imbalance, and irreversible injury. Ischemic strokes are classified into thrombotic and embolic types based on their underlying mechanisms.Thrombotic MechanismsThrombotic stroke develops when a clot forms within a cerebral artery.
01:15Ischemic Stroke ll: Pathophysiology
An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...
01:27Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
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...