P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the
cell membrane that pumps many foreign substances out of cells. More formally, it is an
ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
-dependent
efflux pump with broad
substrate
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (locomotion), the surface over which an organism lo ...
specificity. It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances.
P-gp is extensively distributed and expressed in the
intestinal epithelium where it pumps
xenobiotic
A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
s (such as toxins or drugs) back into the intestinal
lumen, in
liver cells where it pumps them into
bile ducts, in the cells of the
proximal tubule of the kidney where it pumps them into urinary filtrate (in the proximal tubule), and in the
capillary endothelial cells composing the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
and
blood–testis barrier, where it pumps them back into the capillaries.
P-gp is a
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
that in humans is encoded by the ''ABCB1'' gene.
P-gp is a well-characterized
ABC-transporter
The ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans. ABC transp ...
(which transports a wide variety of substrates across extra- and intracellular membranes) of the
MDR MDR may refer to:
Biology
* MDR1, an ATP-dependent cellular efflux pump affording multiple drug resistance
* Mammalian Diving reflex
* Medical device reporting
* Multiple drug resistance, when a microorganism has become resistant to multiple drugs ...
/
TAP subfamily.
The normal excretion of xenobiotics back into the gut lumen by P-gp
pharmacokinetically reduces the
efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...
of some
pharmaceutical drugs (which are said to be P-gp
substrate
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (locomotion), the surface over which an organism lo ...
s). In addition, some
cancer cells also express large amounts of P-gp, further amplifying that effect and rendering these cancers
multidrug resistant. Many drugs inhibit P-gp, typically incidentally rather than as their main
mechanism of action; some foods do as well.
Any such substance can sometimes be called a P-gp inhibitor.
P-gp was discovered in 1971 by
Victor Ling
Victor Ling, (; born 1943) is a Canadian researcher in the field of medicine. Ling's research focuses on drug resistance in cancer. He is best known for his discovery of P-glycoprotein, one of the proteins responsible for multidrug resistance.
...
.
Gene
A 2015 review of polymorphisms in ''ABCB1'' found that "the effect of ''ABCB1'' variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small. Although polymorphisms and haplotypes of ''ABCB1'' have been associated with alterations in drug disposition and drug response, including adverse events with various ABCB1 substrates in different ethnic populations, the results have been majorly conflicting, with limited clinical relevance."
Protein
P-gp is a 170 kDa transmembrane
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
, which includes 10-15 kDa of N-terminal glycosylation. The N-terminal half of the molecule contains 6 transmembrane domains, followed by a large cytoplasmic domain with an ATP-binding site, and then a second section with 6 transmembrane domains and an ATP-binding site that shows over 65% of amino acid similarity with the first half of the polypeptide.
In 2009, the first structure of a mammalian P-glycoprotein was solved (3G5U).
The structure was derived from the mouse MDR3 gene product heterologously expressed in ''Pichia pastoris'' yeast. The structure of mouse P-gp is similar to structures of the bacterial ABC transporter MsbA (3B5W and 3B5X) that adopt an inward facing conformation that is believed to be important for binding substrate along the inner leaflet of the membrane. Additional structures (3G60 and 3G61) of P-gp were also solved revealing the binding site(s) of two different cyclic peptide substrate/inhibitors. The promiscuous binding pocket of P-gp is lined with aromatic amino acid side chains.
Through Molecular Dynamic (MD) simulations, this sequence was proved to have a direct impact in the transporter's structural stability (in the nucleotide-binding domains) and defining a lower boundary for the internal drug-binding pocket.
Species, tissue, and subcellular distribution
P-gp is expressed primarily in certain cell types in the liver, pancreas, kidney, colon, and
jejunum.
P-gp is also found in brain
capillary endothelial cells.
Function
Substrate enters P-gp either from an opening within the
inner leaflet of the membrane or from an opening at the cytoplasmic side of the protein. ATP binds at the cytoplasmic side of the protein. Following binding of each, ATP hydrolysis shifts the substrate into a position to be excreted from the cell. Release of the phosphate (from the original ATP molecule) occurs concurrently with substrate excretion. ADP is released, and a new molecule of ATP binds to the secondary ATP-binding site. Hydrolysis and release of ADP and a phosphate molecule resets the protein, so that the process can start again.
The protein belongs to the superfamily of
ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in
multidrug resistance
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...
. P-gp is an ATP-dependent drug efflux pump for
xenobiotic
A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants.
P-gp transports various substrates across the cell membrane including:
* Drugs such as
colchicine,
desloratadine
Desloratadine (trade names Clarinex and Aerius) is a tricyclic H1 inverse agonist that is used to treat allergies. It is an active metabolite of loratadine.
It was patented in 1984 and came into medical use in 2001.
Medical uses
Desloratad ...
,
tacrolimus and
quinidine.
* Chemotherapeutic agents such as topoisomerase inhibitors (i.e.
etoposide,
doxorubicin), microtubule-targeted drugs (i.e.
vinblastine), and
tyrosine kinase inhibitors
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosph ...
(i.e.
gefitinib,
sunitinib
Sunitinib, sold under the brand name Sutent, is a medication used to treat cancer. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and i ...
).
*
Lipids
*
Steroids
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
*
Xenobiotic
A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
s
*
Peptides
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
*
Bilirubin
Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...
*
Cardiac glycosides like
digoxin
Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is on ...
*
Immunosuppressive agents
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.
Classification
Immunosuppressive drugs can be classified int ...
*
Glucocorticoids like
dexamethasone
* HIV-type 1 antiretroviral therapy agents like
protease inhibitors and
nonnucleoside reverse transcriptase inhibitors
Its ability to transport the above substrates accounts for the many roles of P-gp including:
* Regulating the distribution and bioavailability of drugs
** Increased intestinal expression of P-glycoprotein can reduce the absorption of drugs that are substrates for P-glycoprotein. Thus, there is a reduced bioavailability, and therapeutic plasma concentrations are not attained. On the other hand, supratherapeutic plasma concentrations and drug toxicity may result because of decreased P-glycoprotein
expression
**
Active cellular transport of
antineoplastics resulting in
multidrug resistance
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...
to these drugs
* The removal of toxic metabolites and xenobiotics from cells into
urine, bile, and the intestinal lumen
* The transport of compounds out of the
brain across the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
* Digoxin uptake
* Prevention of
ivermectin and
loperamide entry into the
central nervous system
* The migration of
dendritic cells
* Protection of hematopoietic
stem cells from toxins.
It is inhibited by many drugs, such as
amiodarone,
azithromycin,
captopril
Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inh ...
,
clarithromycin,
cyclosporine,
piperine,
quercetin,
quinidine,
quinine,
reserpine
Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces m ...
,
ritonavir,
tariquidar
Tariquidar (INN/USAN
280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk(于山國)was Ulleungdo(鬱陵島)
Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms ...
, and
verapamil.
Regulation of expression and function of P-gp in cancer cells
At the
transcriptional
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...
level, the expression of P-gp has been intensively studied, and numerous
transcription factors and pathways are known to play roles. A variety of transcription factors, such as
p53,
YB-1,
and
NF-κB are involved in the direct regulation of P-gp by binding to the
promoter regions of the P-gp gene. Many
cell signaling pathways are also involved in transcriptional regulation of P-gp. For example, the
PI3K/Akt pathway
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates A ...
and the
Wnt/β-catenin pathway were reported to positively regulate the expression of P-gp.
Mitogen-activated protein kinase
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to ...
(MAPK) signaling includes three pathways: the classical
MAPK/ERK pathway
The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.
The signal starts when a signaling ...
, the
p38 MAPK pathway
p38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases (MAPKs) that are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell different ...
, and the
c-Jun N-terminal kinase
c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are ...
(JNK) pathway, all of which were reported to have implications in the regulation of the expression of P-gp. Studies suggested that the MAPK/ERK pathway is involved in the positive regulation of P-gp; the p38 MAPK pathway negatively regulates the expression of the P-gp gene; and the JNK pathway was reported to be involved in both positive regulation and negative regulation of P-gp.
After 2008,
microRNAs (miRNAs) were identified as new players in regulating the expression of P-gp in both transcriptional and
post-transcriptional levels. Some miRNAs decrease the expression of P-gp. For example,
miR-200c down-regulates the expression of P-gp through the JNK signaling pathway
or
ZEB1 and
ZEB2;
miR-145
In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
Targets
MicroRNAs are involved in down-reg ...
down-regulates the mRNA of P-gp by directly binding to the
3'-UTR
In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...
of the gene of P-gp and thus suppresses the
translation of P-gp. Some other miRNAs increase the expression of P-gp. For example,
miR-27
miR-27 is a family of microRNA precursors found in animals, including humans. MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The excised region or, ...
a up-regulates P-gp expression by suppressing the
Raf kinase inhibitor protein The Raf kinase inhibitor protein (RKIP) is a kinase inhibitor protein, that regulates many signaling pathways within the cell. RKIP is a member of the phosphatidylethanolamine-binding protein family and has displayed disruptive regulation on the Ra ...
(RKIP); alternatively, miR-27a can also directly bind to the promoter of the P-gp gene, which works in a similar way with the mechanism of action of transcriptional factors.
The expression of P-gp is also regulated by post-translational events, such as
post-transcriptional modification,
degradation, and intracellular trafficking of P-gp.
Pim-1 protects P-gp from
ubiquitination and the following degradation in the
proteasome
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases.
Proteasomes are part of a major mechanism by w ...
.
Small GTPases
Rab5 down-regulates the
endocytotic trafficking of P-gp and thus increases the functional P-gp level on the
cell membrane; while Small GTPases
Rab4 work in an opposite way: Rab4 down-regulates the
exocytotic trafficking of P-gp from
intracellular compartments
Cellular compartments in cell biology comprise all of the closed parts within the cytosol of a eukaryotic cell, usually surrounded by a single or double lipid layer membrane. These compartments are often, but not always, defined as membrane-b ...
to the cell membrane, and therefore decreases the functional P-gp level on the cell membrane.
Clinical significance
Drug interactions
Some common pharmacological inhibitors of P-glycoprotein include:
amiodarone,
clarithromycin,
ciclosporin,
colchicine,
diltiazem
Diltiazem, sold under the brand name Cardizem among others, is a calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be used ...
,
erythromycin
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...
,
felodipine,
ketoconazole
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...
,
lansoprazole
Lansoprazole, sold under the brand name Prevacid among others, is a medication which reduces stomach acid. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. Effectiveness is similar to ...
,
omeprazole and other
proton-pump inhibitors,
nifedipine,
paroxetine,
reserpine
Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces m ...
,
saquinavir,
sertraline,
quinidine,
tamoxifen,
verapamil,
and
duloxetine.
Elacridar and
CP 100356
CP, cp. or its variants may refer to:
Arts, entertainment, and media
* Cariyapitaka (Cp), a canonical Buddhist story collection
* The Canadian Press, a Canadian news agency
* Child pornography
* '' The Christian Post'', an American newspaper
* ...
are other common P-gp inhibitors.
Zosuquidar
Zosuquidar (development code LY-335979) is an experimental antineoplastic drug. Zosquidir inhibits P-glycoproteins. Other drugs with this mechanism include tariquidar and laniquidar. P-glycoproteins are trans-membrane proteins that pump fo ...
and
tariquidar
Tariquidar (INN/USAN
280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk(于山國)was Ulleungdo(鬱陵島)
Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms ...
were also developed with this in mind. Lastly,
valspodar
Valspodar (PSC833) is an experimental cancer treatment and chemosensitizer. It is a derivative of ciclosporin D (cyclosporin D).
Its primary use is as an inhibitor of the efflux transporter P-glycoprotein. Previous studies in animal models have ...
and
reversan are other examples of such agents. ABCB1 is linked to the daily dose of
warfarin required to maintain the INR to a target of 2.5. Patients with the GT or TT genotypes of the 2677G>T SNP require around 20% more warfarin daily.
Common pharmacological inducers of P-glycoprotein include
carbamazepine,
dexamethasone,
doxorubicin,
nefazodone,
phenobarbital,
phenytoin,
prazosin
Prazosin is an α1 blocker medication primarily used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is a less preferred treatment of high blood pressure. Other ...
,
rifampicin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. ...
,
St. John's wort,
tenofovir,
tipranavir
Tipranavir (TPV), or tipranavir disodium, is a nonpeptidic protease inhibitor (PI) manufactured by Boehringer Ingelheim under the trade name Aptivus . It is administered with ritonavir in combination therapy to treat HIV infection.
Tipranavir ...
,
trazodone, and
vinblastine.
Substrates of P-glycoprotein are susceptible to changes in pharmacokinetics due to drug interactions with P-gp inhibitors or inducers. Some of these substrates include
colchicine,
ciclosporin,
dabigatran,
digoxin
Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is on ...
,
diltiazem
Diltiazem, sold under the brand name Cardizem among others, is a calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be used ...
,
fexofenadine,
indinavir,
morphine, and
sirolimus.
Diseases (non-cancer)
Decreased P-gp expression has been found in
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
brains.
Altered P-gp function has also been linked to
inflammatory bowel diseases (IBD);
however, due to its ambivalent effects in intestinal inflammation many questions remain so far unanswered.
While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD.
Mice deficient in MDR1A develop chronic intestinal inflammation spontaneously, which appears to resemble human
ulcerative colitis.
Cancer
P-gp efflux activity is capable of lowering intracellular concentrations of otherwise beneficial compounds, such as chemotherapeutics and other medications, to sub-therapeutic levels. Consequently, P-gp overexpression is one of the main mechanisms behind decreased intracellular drug accumulation and development of multidrug resistance in human multidrug-resistant (MDR) cancers.
History
P-gp was first characterized in 1976. P-gp was shown to be responsible for conferring multidrug resistance upon mutant cultured cancer cells that had developed resistance to cytotoxic drugs.
The structure of mouse P-gp, which has 87% sequence identity to human P-gp, was resolved by
x-ray crystallography in 2009.
The first structure of human P-gp was solved in 2018, with the protein in its ATP-bound, outward-facing conformation.
Research
Radioactive
verapamil can be used for measuring P-gp function with
positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
.
P-gp is also used to differentiate
transitional B cells Transitional B cells are B cells at an intermediate stage in their development between bone marrow immature cells and mature B cells in the spleen. Primary B cell development takes place in the bone marrow, where immature B cells must generate a fun ...
from naive B cells. Dyes such as
rhodamine 123 and MitoTracker dyes from
Invitrogen can be used to make this differentiation.
MDR1 as a drug target
It has been suggested that
MDR1 inhibitor
P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
s might treat various diseases, especially cancers, but none have done well in clinical trials.
''Inhibiting Cancer Drug Resistance Gene May Not Be Best Approach'' Apr 2020
/ref>
Single nucleotide polymorphism ''rs1045642''
Single Nucleotide Polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
are important for the differential activity of the PGP pump.
Homozygous subjects, identified with the TT genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
, are usually more able to extrude xenobiotics from the cell. A Homozygous genotype for the allele ABCB1/MDR1 is capable of a higher absorption from the blood vessels and a lower extrusion into the lumen.
Xenobiotics are extruded at a lower rate with heterozygous (CT) alleles compared to homozygous ones.
References
Further reading
*
*
External links
*
*
*
{{DEFAULTSORT:P-Glycoprotein
ATP-binding cassette transporters
Clusters of differentiation