Редактирование: ABCB1

ATP-dependent translocase ABCB1 (ATP-binding cassette sub-family B member 1) (Multidrug resistance protein 1) (EC 7.6.2.2) (P-glycoprotein 1) (Phospholipid transporter ABCB1) (EC 7.6.2.1) (CD243 antigen) [MDR1] [PGY1]

==Publications==

{{medline-entry
|title=Paclitaxel-induced sensory peripheral neuropathy is associated with an [[ABCB1]] single nucleotide polymorphism and older age in Japanese.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28447211
|abstract=Whether age and inter-individual variability of pharmacogenetics are risk factors for paclitaxel-induced peripheral neuropathy (PIPN) is inconclusive. This study was conducted to evaluate the influence of previously investigated single nucleotide polymorphisms (SNPs) and age, using genotype data from a prospective study of paclitaxel-related toxicity in Japanese patients with breast cancer. Peripheral blood mononuclear cells from 127 Japanese women with breast cancer who received weekly adjuvant paclitaxel were used to genotypes [[SLCO1B3]] T334G (rs4149117), [[CYP2C8]] A1196G (rs10509681), [[ABCB1]] C1236T (rs1128503), [[ABCB1]] G2677T/A (rs2032582), and [[ABCB1]] C3435T (rs1045642). Genotypic and clinical factors were investigated for associations with PIPN. Of the five SNPs evaluated, no SNPs were significantly associated with grade 2 or higher PIPN. However, [[ABCB1]] 1236 TT showed a trend to associate with grade 2 or higher PIPN compared to [[ABCB1]] CT/CC (odds ratio 2.1, 95% CI 0.991-4.548, p = 0.051). In subgroup analysis, patients ≥60 years old with an [[ABCB1]] 1236 TT had a higher incidence of ≥grade 2 PIPN compared to patients with CT or CC genotype (p = 0.027). On multivariable analysis, age ≥60 years and the [[ABCB1]] 1236 TT showed a significant association with ≥grade 2 PIPN (p = 0.005 and p = 0.034, respectively). [[ABCB1]] 1236 TT genotype and older age might be a predictor of PIPN, which diminishes quality of life of cancer survivors.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* Adult
* Aged
* Aging
* Antineoplastic Agents, Phytogenic
* Asian Continental Ancestry Group
* Breast Neoplasms
* Cytochrome P-450 CYP2C8
* Female
* Genotype
* Humans
* Incidence
* Middle Aged
* Organic Anion Transporters, Sodium-Independent
* Paclitaxel
* Peripheral Nervous System Diseases
* Pharmacogenetics
* Polymorphism, Single Nucleotide
* Predictive Value of Tests
* Prospective Studies
* Sensory Receptor Cells
* Solute Carrier Organic Anion Transporter Family Member 1B3
|keywords=* ABCB1
* CYP2C8
* Older age
* Paclitaxel-induced peripheral neuropathy
* SLCO1B3
|full-text-url=https://sci-hub.do/10.1007/s00280-017-3314-9
}}
{{medline-entry
|title=Relationship between mRNA expression levels of [[CYP3A4]], [[CYP3A5]] and SXR in peripheral mononuclear blood cells and aging in young kidney transplant recipients under tacrolimus treatment.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25916520
|abstract=The activity of several key enzymes involved in the metabolism of many drugs is subject to change closely related to the age of patients. This possibility must also be considered in the case of tacrolimus, the most important calcineurins inhibitor, which is widely used in pediatric kidney transplantation. As well as in the liver and intestine, some of the enzymes involved in the metabolism of tacrolimus were also isolated in the peripheral blood mononuclear cells (PBMCs), where also appear to play an important regulatory action. Therefore, the influence of some external factors on the expression of specific mRNA can be determined noninvasively. The correlation between the levels of mRNA specific for key enzymes SXR, CYP3A and [[ABCB1]] involved in the metabolism of tacrolimus was evaluated in PBMCs obtained from a selected population of 29 young kidney transplant recipients. A possible correlation between the expression of these specific mRNAs and tacrolimus pharmacokinetics was also investigated. The patients' age and their blood concentrations of SXR mRNA were directly correlated with the expression of [[CYP3A4]], [[CYP3A5]] mRNAs, but not of [[ABCB1]] mRNA in the PBMCs. tacrolimus-normalized daily dose was strongly correlated with patient's age and multivariable regression indicates the [[CYP3A4]]-specific mRNA as the sole independent variable influencing tacrolimus concentration-to-dose ratio. Aging and SXR mRNA significantly affect the expression of [[CYP3A4]]- and [[CYP3A5]]-specific mRNA as measured by their concentration in PBMC.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* Adolescent
* Aging
* Cytochrome P-450 CYP3A
* Female
* Humans
* Immunosuppressive Agents
* Kidney Transplantation
* Male
* Monocytes
* Pregnane X Receptor
* RNA, Messenger
* Receptors, Steroid
* Tacrolimus
|keywords=* ABCB1
* CYP3A4
* CYP3A5
* SXR
* mRNA
* pediatric kidney transplant
* peripheral blood mononuclear cells
* tacrolimus
|full-text-url=https://sci-hub.do/10.2217/pgs.15.18
}}
{{medline-entry
|title=Vascular and extravascular distribution of the ATP-binding cassette transporters [[ABCB1]] and ABCC1 in aged human brain and pituitary.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25218792
|abstract=ATP-binding cassette (ABC) transporters play an increasing role in the understanding of pathologic peptide deposition in neurodegenerative diseases (NDs), such as Alzheimer's and Parkinson's. To describe the location of the most important ABC transporters for NDs in human brain tissue, we investigated [[ABCB1]] and ABCC1 immunohistologically in the adult human brain and pituitary. Both transporters have similar but not identical expression patterns. In brain regions with an established blood-brain barrier (BBB), [[ABCB1]] and ABCC1 were ubiquitously expressed in endothelial cells of the microvasculature and in a subset of larger blood vessels (mostly venules). Remarkably, both transporters were also found in fenestrated capillaries in circumventricular organs where the BBB is absent. Moreover, [[ABCB1]] and ABCC1 were also expressed in various non-endothelia cells such as pericytes, astrocytes, choroid plexus epithelia, ventricle ependymal cells, and neurons. With regard to their neuronal expression it was shown that both transporters are located in specific nerve cell populations, which are also immunopositive for three putative cell markers of purinergic cell signalling, namely 5'-nucleotidase, adenosine deaminase and nucleoside triphosphate diphosphohydrolase-2. Therefore, we speculate that neuronal expression of [[ABCB1]] and ABCC1 might be linked to adenosinergic/purinergic neuromodulation. Lastly, both transporters were observed in multiple adenohypophyseal cells. 
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* Adult
* Aging
* Blood-Brain Barrier
* Female
* Gene Expression Regulation
* Humans
* Male
* Middle Aged
* Multidrug Resistance-Associated Proteins
* Nerve Tissue Proteins
* Pituitary Gland
|keywords=* ABC transporters
* ATP-binding cassette sub-family B member 1 (ABCB1)
* ATP-binding cassette sub-family C member 1 (ABCC1)
* Blood–brain barrier
* Circumventricular organs
* Human brain
* Human pituitary
* Neurons
* Purinergic signalling
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310818
}}
{{medline-entry
|title=Age and [[CYP3A5]] genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21930396
|abstract=Tacrolimus is one of the commonly used immunosuppressive drugs for pediatric heart transplants. Large variation exists in pharmacokinetics during the direct post-transplant period, resulting in an increased risk of adverse events. Limited data are available on the interaction of age, [[CYP3A5]] and [[ABCB1]] genotype, and disease severity on the variation in disposition and outcome in pediatric heart transplant recipients. We studied the relationship between age and [[CYP3A5]] and [[ABCB1]] genotype and the Pediatric Risk of Mortality (PRISM) score on tacrolimus dose (mg/kg), steady-state trough concentrations, and concentration/dose ratio, as well as rejection and renal function for 14 days after heart transplant in children. Tacrolimus was administered to 39 children (median age, 6.0 years) after transplant. A correlation was found between the age at the time of transplant and the tacrolimus dosing requirements (r(s) = -0.447, p = 0.004) and the concentration/dose ratio (r(s) = 0.351, p = 0.029). [[CYP3A5]] expressors required median (interquartile range) higher doses of tacrolimus (0.14 [0.09] vs 0.06 [0.04] mg/kg/12 hours, p = 0.001), and had lower concentration/dose ratios (45.34 [44.54] vs 177.78 [145.38] ng/ml per mg/kg/12 hours, p < 0.0001). This relationship was not seen with the [[ABCB1]] genotype. Age and [[CYP3A5]] genotype predicted the tacrolimus dosing requirements as well as the concentration/dose ratio (R(2) = 0.351, p = 0.001 and R(2) = 0.521, p < 0.001). No relationship was found between any of the [[CYP3A5]] or [[ABCB1]] genotypes and the estimated glomerular filtration rate. Younger age and [[CYP3A5]] expressor genotype were independently associated with higher dosing requirements and lower tacrolimus concentration/dose ratios.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* ATP Binding Cassette Transporter, Subfamily B, Member 1
* Aging
* Child
* Cytochrome P-450 CYP3A
* Dose-Response Relationship, Drug
* Female
* Genotype
* Glomerular Filtration Rate
* Graft Rejection
* Heart Transplantation
* Humans
* Immunosuppressive Agents
* Kidney
* Male
* Retrospective Studies
* Severity of Illness Index
* Tacrolimus
* Time Factors
* Treatment Outcome

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640375
}}
{{medline-entry
|title=[[ABCB1]] (MDR1) polymorphisms and antidepressant response in geriatric depression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20555295
|abstract=Variation in the ATP-binding cassette, subfamily B, member 1 transporter ([[ABCB1]]) (multidrug-resistance gene 1) gene has been investigated as a predictor of response to treatment with a variety of medications such as antiarrhythmics, chemotherapeutic agents, anti-HIV medications, and some psychotropics. The [[ABCB1]] gene product, P-glycoprotein, affects the transport of drugs out of many cell types, including endothelial cells at the blood-brain barrier. We sought to determine if [[ABCB1]] polymorphisms predict response to antidepressant treatment in geriatric patients. We compared the effects of [[ABCB1]] genetic variation on the therapeutic response to paroxetine, a P-glycoprotein substrate, and to mirtazapine, which is not thought to be transported by [[ABCB1]], in a sample of 246 elderly patients with major depression treated in a clinical trial setting. A total of 15 single nucleotide polymorphisms in the [[ABCB1]] gene were assessed in each patient. Two of these [[ABCB1]] single nucleotide polymorphisms were earlier reported to predict treatment response in patients prescribed with P-glycoprotein substrate antidepressants. The two earlier identified [[ABCB1]] markers for antidepressant response predicted time to remission in our paroxetine-treated patients, but not in the mirtazapine-treated patients. These results replicate the published findings of others. If a Bonferroni correction for type I error is made, our results do not reach the criteria for statistical significance. However, the Bonferroni correction may be too conservative given the strong linkage disequilibrium among some of the markers and our aim to replicate the earlier published findings. Our study provides confirmation that certain [[ABCB1]] polymorphisms predict response to substrate medications in geriatric patients.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* ATP Binding Cassette Transporter, Subfamily B, Member 1
* Aged
* Aging
* Antidepressive Agents
* Depression
* Female
* Genotype
* Humans
* Japan
* Male
* Paroxetine
* Polymorphism, Single Nucleotide
* Survival Analysis
* Treatment Outcome

|full-text-url=https://sci-hub.do/10.1097/FPC.0b013e32833b593a
}}
{{medline-entry
|title=Genetic factors associated with drug-resistance of epilepsy: relevance of stratification by patient age and aetiology of epilepsy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20064729
|abstract=Epilepsy drug-resistance may depend on the metabolism of antiepileptic drugs (AEDs), transport to the epileptic focus and/or target sensitivity. Furthermore, drug response depends on multiple characteristics of the patient, the epilepsy, and the antiepileptic drugs used. We have investigated the association between polymorphisms related to antiepileptic drug metabolism (CYP2C9, [[CYP2C19]], and UGT), transport ([[ABCB1]]), and targets (SCN1A) both in a crude analysis and after adjusting by clinical factors associated with drug-resistance, and stratifying by patient age or aetiology of epilepsy. Caucasian outpatients (N=289), children (N=80) and adolescent-adults (N=209), with idiopathic (N=69), cryptogenic (N=97) or symptomatic epilepsies (N=123) were selected when they had either drug-resistance (with at least four seizures over the previous year after treatment with more than three appropriate AEDs at appropriate doses) or drug responsiveness (without seizures for at least a year). Samples were genotyped by allelic discrimination using TaqMan probes. No significant association between polymorphisms and drug-resistance was found either in the crude analysis or in the adjusted analysis. However, adults with the [[ABCB1]]_3435TT or 2677TT genotypes had a lower risk of drug-resistance than those with the CC or the GG genotypes. Furthermore, patients with symptomatic epilepsies with the [[ABCB1]]_3435CT or TT genotypes had a lower risk of drug-resistance than those with the CC genotype. An opposite but insignificant tendency was found in children and in idiopathic epilepsies. Although replication studies will be needed to confirm our results, they suggest that stratification by patient age and by the aetiology of epilepsy could contribute to unmask the association between [[ABCB1]] polymorphisms and drug-resistance of epilepsy.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* ATP Binding Cassette Transporter, Subfamily B, Member 1
* Adolescent
* Adult
* Aging
* Anticonvulsants
* Aryl Hydrocarbon Hydroxylases
* Child
* Child, Preschool
* Cytochrome P-450 CYP2C19
* Cytochrome P-450 CYP2C9
* Drug Resistance
* Epilepsy
* Female
* Gene Frequency
* Genetic Predisposition to Disease
* Genotype
* Glucuronosyltransferase
* Humans
* Male
* Middle Aged
* NAV1.1 Voltage-Gated Sodium Channel
* Nerve Tissue Proteins
* Odds Ratio
* Polymorphism, Single Nucleotide
* Sodium Channels
* Young Adult

|full-text-url=https://sci-hub.do/10.1016/j.seizure.2009.12.004
}}
{{medline-entry
|title=A double-negative (IgD-[[CD27]]-) B cell population is increased in the peripheral blood of elderly people.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/19698733
|abstract=The T cell branch of the immune system has been extensively studied in the elderly and it is known that the elderly have impaired immune function, mainly due to the chronic antigenic load that ultimately causes shrinkage of the T cell repertoire and filling of the immunologic space with memory T cells. In the present paper, we describe the IgD(-)[[CD27]](-) double-negative B cell population which (as we have recently described) is higher in the elderly. Most of these cells were IgG( ). Evaluation of the telomere length and expression of the [[ABCB1]] transporter and anti-apoptotic molecule, Bcl2, shows that they have the markers of memory B cells. We also show that these cells do not act as antigen presenting cells, as indicated by the low levels of [[CD80]] and DR, nor do they express significant levels of the [[CD40]] molecule necessary to interact with T lymphocytes through the ligand, CD154. Hence, we hypothesize that these expanded cells are late memory or exhausted cells that have down-modulated the expression of [[CD27]] and filled the immunologic space in the elderly. These cells might be the age-related manifestation of time-enduring stimulation or dysregulation of the immune system.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* ATP Binding Cassette Transporter, Subfamily B, Member 1
* Adult
* Age Factors
* Aged
* Aged, 80 and over
* Aging
* Antigens, CD19
* B-Lymphocyte Subsets
* B7-1 Antigen
* CD40 Antigens
* Cells, Cultured
* Flow Cytometry
* HLA-DR Antigens
* Humans
* Immunoglobulin D
* Immunologic Memory
* Ki-67 Antigen
* Middle Aged
* Proto-Oncogene Proteins c-bcl-2
* Telomere
* Tumor Necrosis Factor Receptor Superfamily, Member 7
* Young Adult

|full-text-url=https://sci-hub.do/10.1016/j.mad.2009.08.003
}}
{{medline-entry
|title=A drug transporter for all ages? [[ABCB1]] and the developmental pharmacogenetics of cyclosporine.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18518855
|abstract=Evaluation of: Fanta S, Niemi M, Jönsson S et al.: Pharmacogenetics of cyclosporine in children suggests an age-dependent influence of [[ABCB1]]polymorphisms. Pharmacogenet. Genomics 18(2), 77-90 (2008). The clinical use of the immunosuppressive agent cyclosporine is complicated by its toxicity, narrow therapeutic window and highly variable pharmacokinetics between individuals. In adults, genetic polymorphisms in the genes encoding the cyclosporine-metabolizing enzymes [[CYP3A4]] and [[CYP3A5]], as well as the [[ABCB1]] gene, which encodes the efflux-pump P-glycoprotein, seem to have a limited effect, if any, on cyclosporine pharmacokinetics. However, the authors have now reported for the first time an association between cyclosporine oral bioavailability and the [[ABCB1]] c.1236C>T and c.2677G>T polymorphisms, as well as the related haplotype c.1199G-c.1236C-c.2677G-c.3435C, in children with end-stage renal disease older than 8 years of age. Carriers of the variant alleles had a cyclosporine oral bioavailability that was around 1.5-times higher compared with noncarriers. This association was not observed in children younger than 8 years of age. In addition, no relation between cyclosporine disposition and genetic variation in the [[CYP3A4]], [[CYP3A5]], [[ABCC2]], [[SLCO1B1]] and [[NR1I2]] genes was observed. These data suggest that the effect of [[ABCB1]] polymorphisms on cyclosporine pharmacokinetics is related to age, and thus developmental stage. Although further study is necessary to establish the predictive value of [[ABCB1]] genotyping for individualization of cyclosporine therapy in children older than 8 years, an important step towards further personalized immunosuppressive drug therapy has been made.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* ATP Binding Cassette Transporter, Subfamily B, Member 1
* Adult
* Aging
* Child
* Cyclosporine
* Humans
* Immunosuppressive Agents
* Inactivation, Metabolic
* Kidney Transplantation
* Pharmacogenetics
* Polymorphism, Single Nucleotide

|full-text-url=https://sci-hub.do/10.2217/14622416.9.6.783
}}
{{medline-entry
|title=Independent regulation of [[ABCB1]] and ABCC activities in thymocytes and bone marrow mononuclear cells during aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17635801
|abstract=Aging modifies a number of functional and phenotypic parameters of cells from the immune system. In this study, the activities of two members of the superfamily of ATP-binding cassette (ABC) transport proteins, [[ABCB1]] and ABCC (measured by rhodamine 123 efflux and Fluo-3 efflux respectively), were compared in murine bone marrow cells and thymocytes of young (3-4 weeks old), adult (2-3 months old) and old (18 months old) mice. [[ABCB1]] activity was shown to be age regulated in murine bone marrow mononuclear cells and thymocytes. In the bone marrow, the increased amount of cells with [[ABCB1]] activity observed in old mice was restricted to the c-kit(-)Sca-1( ) and c-kit( )Sca-1( ) subpopulations. Only a small percentage of c-kit( ) cells in the thymus had [[ABCB1]] activity, and this subpopulation increased with age. In the thymus, old age augmented this activity in the CD4(-) CD8(-) double-negative cells and in the CD4( ) and CD8( ) single-positive populations. The activity of another ABC transporter, the ABCC-related activity, was also modified by age in the bone marrow. However, the age-related increase was observed in the subpopulations were [[ABCB1]] was not modified, namely the non-progenitor population (c-kit(-)Sca-1(-)cells) and c-kit( )Sca-1(-) cells. Nearly, all thymocytes expressed the [[ABCC1]] molecule in an active form and aging did not affect this pattern. This study demonstrates an independent upregulation of [[ABCB1]] and ABCC activities during the aging process. The increases were observed in different subsets of cells but followed a developmentally regulated pattern. The functions played by these transporters and alterations in aging are discussed.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* ATP Binding Cassette Transporter, Subfamily B, Member 1
* ATP-Binding Cassette Transporters
* Aging
* Animals
* Bone Marrow Cells
* Cells, Cultured
* Hematopoietic Stem Cells
* Leukocytes, Mononuclear
* Male
* Mice
* Mice, Inbred C57BL
* Multidrug Resistance-Associated Proteins
* Thymus Gland

|full-text-url=https://sci-hub.do/10.1111/j.1365-3083.2007.01965.x
}}
{{medline-entry
|title=A study of genetic ([[CYP2D6]] and [[ABCB1]]) and environmental (drug inhibitors and inducers) variables that may influence plasma risperidone levels.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17541883
|abstract=Risperidone (R) is metabolized to 9-hydroxyrisperidone (9-OHR) by cytochrome P450 2D6 ([[CYP2D6]]). The main objective of this naturalistic study was to investigate the variables associated with two plasma ratios: the plasma R:9-OHR concentration ratio and the total concentration-to-dose (C:D) ratio. These ratios were studied as continuous measures by linear regression analyses and as three dichotomous variables in logistic regression analyses: R:9-OHR ratio >1 (indicative of lack of [[CYP2D6]] activity), C:D ratio >14 (indicative of diminished R elimination), and C:D ratio <3.5 (indicative of increased R elimination). Plasma R levels; genotypes for [[CYP2D6]], [[CYP3A5]]; and [[ABCB1]] genes, and co-medication, including CYP inhibitors and CYP3A inducers, were studied in 277 patients. Almost all [[CYP2D6]] poor metabolizers (PMs) had an inverted R:9-OHR ratio (>1). Having a [[CYP2D6]] PM phenotype was strongly associated with a C:D ratio >14 (OR=8.2; 95% confidence interval [CI]=2.0-32.7), indicating diminished R elimination. [[CYP2D6]] ultrarapid metabolizers (UMs) did not exhibit an increased R elimination. Some [[ABCB1]] (or MDR1) variants were significantly associated with increased R:9-OHR ratios and decreased C:D ratios, but the results were neither consistent nor robust. Taking CYP inhibitors was significantly associated with a C:D ratio >14 (OR=3.8; CI=1.7-8.7) and with an inverted R:9-OHR ratio. Taking CYP3A inducers was significantly associated with a C:D ratio <3.5 (OR=41.8; CI=12.7-138), indicating increased R elimination. Female gender and old age appeared to be associated with a lower R elimination. Our study indicated that the [[CYP2D6]] PM phenotype may have a major role in personalizing R doses, whereas the [[CYP3A5]] PM phenotype probably has no role. CYP inducers and inhibitors appear to be relevant to R dosing. New studies are needed, particularly to further assess the role of the [[CYP2D6]] UM phenotype and [[ABCB1]] variants in R pharmacokinetics.
|mesh-terms=* ATP Binding Cassette Transporter, Subfamily B
* ATP Binding Cassette Transporter, Subfamily B, Member 1
* Adult
* Aging
* Antipsychotic Agents
* Cytochrome P-450 CYP2D6
* Cytochrome P-450 CYP2D6 Inhibitors
* Cytochrome P-450 CYP3A
* Cytochrome P-450 Enzyme Inhibitors
* Cytochrome P-450 Enzyme System
* Drug Interactions
* Enzyme Induction
* Female
* Humans
* Isoxazoles
* Linear Models
* Male
* Middle Aged
* Organic Anion Transporters
* Paliperidone Palmitate
* Pyrimidines
* Risperidone
* Sex Factors

|full-text-url=https://sci-hub.do/10.1055/s-2007-973836
}}
{{medline-entry
|title=Adenosine triphosphate-binding cassette transporter genes in ageing and age-related diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12437993
|abstract=The family of adenosine triphosphate (ATP)-binding cassette (ABC) transporters is the largest gene family known. While some ABC transporters translocate single substances across membranes with high specificity, others transport a wide variety of different lipophilic compounds. They are responsible for many physiological processes and are also implicated in a number of diseases. The present review focuses on ABC transporter genes which are involved in ageing and age-related diseases. Expression of [[ABCB1]] (MDR1, P-glycoprotein) increases with age in CD4( ) and CD8( ) T-lymphocytes indicating that P-glycoprotein may be involved in the secretion of cytokines, growth factors, and cytotoxic molecules. As T cells in aged individuals are hyporesponsive leading to a reduced immunodefence capability, a role of [[ABCB1]] in age-related immunological processes is presumed. The [[ABCA1]] (ABC1) gene product translocates intracellular cholesterol and phospholipids out of macrophages. Genetic aberrations in [[ABCA1]] cause perturbations in lipoprotein metabolism and contribute to atherosclerosis. [[ABCA4]] (ABCR) represents a retina-specific ABC transporter expressed in rod photoreceptor cells. The [[ABCA4]] gene product translocates retinyl-derivatives. Mutations in the [[ABCA4]] gene contribute to age-related macular degeneration. Polymorphisms in the sulfonylurea receptor gene (ABCC8, SUR1) are associated with non-insulin-dependent diabetes mellitus (NIDDM). Sulfonylureas inhibit potassium conductance and are used to treat NIDDM by stimulation of insulin secretion across ATP-sensitive potassium channels in pancreatic beta-cell membranes. Possible diagnostic and therapeutic implications of ABC transporters for age-related diseases are discussed.
|mesh-terms=* ATP-Binding Cassette Transporters
* Aging
* Animals
* Arteriosclerosis
* Diabetes Mellitus, Type 2
* Gene Expression Regulation
* Humans
* Macular Degeneration

|full-text-url=https://sci-hub.do/10.1016/s1568-1637(02)00046-6
}}