G
Genetic Archaeology
GENETIC ARCHAEOLOGY // PROFILE

ABCB1

ATP-Binding Cassette Subfamily B Member 1

CHR 7
7q21.12

Overview

The ABCB1 gene (also known as MDR1 – Multi-Drug Resistance 1) encodes P-glycoprotein (P-gp), the most important active transporter for drugs and toxins. It determines the blood-brain barrier and the availability of many psychotropic drugs.

📍 Position
7q21.12 (Chromosome 7)
🏷️ Category
Metabolism
⚡ Function
ATP-dependent efflux transporter
📊 Frequency
T-allele ~40-60%

Function of P-Glycoprotein

P-glycoprotein is a membrane transporter that pumps substances out of the cell:

Key Functions:

🧠 Blood-Brain Barrier

P-gp in brain capillaries pumps drugs and toxins back into the blood. It protects the brain but also reduces the effectiveness of certain medications.

🛡️ Multidrug Resistance

In cancer cells, excess P-gp can pump out chemotherapeutic agents, leading to resistance.

💡 ABCB1 Substrates: Over 200 substances! Including antidepressants (citalopram, venlafaxine), antiepileptics, immunosuppressants (cyclosporine), statins, digoxin, and many more.

🧬 Genetic Variant

rs1045642 (C3435T)
7:87138645
Higher Activity

C

/

Lower Activity

T

C3435T (Ile1145=): Although a synonymous SNP (no amino acid change), it significantly affects mRNA stability and protein expression.

C/C or C/T
Normal to high ABCB1 activity. More drug export from the brain. Lower brain levels.
T/T (20-25%)
Reduced ABCB1 activity. Higher drug levels in the brain. Potentially more central side effects.
⚠️ Clinical Significance: The T/T genotype can lead to higher brain levels of psychotropic drugs—which may be more effective but also cause more side effects. CC/CT often shows treatment resistance in depression due to lower brain levels.

💊 Drug Interactions

Drug Groups Influenced by ABCB1:

Psychotropic Drugs:

  • Citalopram, Escitalopram
  • Sertraline, Venlafaxine
  • Amitriptyline, Nortriptyline
  • Haloperidol, Risperidone
  • Alprazolam
Other Substrates:

  • Statins (Atorvastatin, Simvastatin)
  • Digoxin
  • Cyclosporine, Tacrolimus
  • Loperamide
  • Ca-channel blockers
✅ P-gp Inhibitors (increase drug levels): Grapefruit juice, verapamil, clarithromycin, itraconazole, hypericin (St. John’s wort). Inducers (lower levels): Rifampicin, St. John’s wort, carbamazepine.

🧠 Psychiatric Applications

T/T Genotype

  • Higher brain levels of antidepressants
  • Better efficacy at lower doses
  • Higher risk of central side effects
  • Possibly more initial side effects

C-Carrier (with C-allele)

  • Lower brain levels
  • Higher doses may be required
  • Increased risk of treatment failure
  • P-gp combination with inducers is problematic

📚 Data Sources

  • OMIM: #171050 (ABCB1/MDR1 Gene)
  • dbSNP: rs1045642 (C3435T)
  • PubMed: Hoffmeyer et al. (2000) – Functional polymorphisms of MDR1
  • Clinical Pharmacology: ABCB1 and drug response
  • Pharmacogenomics Journal: ABCB1 in psychiatry

Last Update: February 2026

Biological Function

P-Glycoprotein transports a variety of substances out of cells, including many medications (e.g., antidepressants, antiepileptics, immunosuppressants, cancer drugs). The C3435T variant (rs1045642) influences transporter expression and activity. TT genotype often shows lower ABCB1 activity, potentially leading to increased drug levels in the brain and more side effects.

Associated Conditions

Multidrug Resistance (Cancer) Side effects of psychotropic drugs Therapy resistance in depression Collagen vascular disease
Molecular Analysis

Analyzed Markers

rs1045642 Pharmacogenetic
Pos: 7:87138645 | Alleles: C/T

C3435T in Exon 26 - Synonymous SNP, but affects mRNA stability and protein expression. CC: higher ABCB1 activity (more drug export, lower brain levels). TT: reduced activity (higher brain levels, more side effects).