The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy
Zoran Sterjev1, Gordana Kiteva Trencevska2, Emilija Cvetkovska2, Igor Petrov2, Igor Kuzmanovski2, Jasmina T Ribarska3, Aleksandra K Nestorovska1, Nadica Matevska1, Zorica Naumovska1, Suzana Jolevska-Trajkovic3, Aleksandar Dimovski1, Ljubica Suturkova11Institute of Pharmaceutical Chemistry, Faculty o...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/6ba46e269dde456294c428af6f671628 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:6ba46e269dde456294c428af6f671628 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:6ba46e269dde456294c428af6f6716282021-12-02T04:47:46ZThe association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy1176-63281178-2021https://doaj.org/article/6ba46e269dde456294c428af6f6716282012-04-01T00:00:00Zhttp://www.dovepress.com/the-association-of-c3435t-single-nucleotide-polymorphism-pgp-glycoprot-a9735https://doaj.org/toc/1176-6328https://doaj.org/toc/1178-2021Zoran Sterjev1, Gordana Kiteva Trencevska2, Emilija Cvetkovska2, Igor Petrov2, Igor Kuzmanovski2, Jasmina T Ribarska3, Aleksandra K Nestorovska1, Nadica Matevska1, Zorica Naumovska1, Suzana Jolevska-Trajkovic3, Aleksandar Dimovski1, Ljubica Suturkova11Institute of Pharmaceutical Chemistry, Faculty of Pharmacy Skopje, Republic of Macedonia; 2Clinic of Neurology, Faculty of Medicine, Skopje, Republic of Macedonia; 3Institute of Pharmaceutical Analysis, Faculty of Pharmacy Skopje, Republic of MacedoniaAbstract: The ABCB1 gene encodes the P-glycoprotein (Pgp) protein, which is thought to transport various antiepileptic drugs. The single nucleotide polymorphism (SNP) (C3435T) in exon 26 of this gene correlates with the altered expression levels of P-glycoprotein, range of drug response and clinical conditions. In order to investigate the influence of this polymorphism on the susceptibility to and efficacy of carbamazepine therapy, we evaluated the allelic frequency and genotype distribution of this variant in 162 epilepsy patients from the Republic of Macedonia. Statistically significant differences were detected neither in the allelic frequency and genotype distribution between carbamazepine-resistant and carbamazepine-responsive epilepsy patients nor between the subgroups of carbamazepine (CBZ)-responsive patients treated with different CBZ doses. However, the T-allele was enriched in CBZ-responsive patients who required higher maintenance CBZ doses, This observation was substantiated by the findings that the median total plasma levels were the lowest in patients with CC (20 µmol/L) followed by CT (23 µmol/L) and TT (29 µmol/L) genotypes. Patients with a CC genotype also had a higher likelihood of response compared to patients with CT or TT genotypes over a wide range (400–1000 mg/day) of initial doses of CBZ. The T allele showed a reduced expression of ~5% compared to the C allele in peripheral blood mononuclear cells in heterozygotes for the variant. This difference might be translated into ~10% difference in homozygotes for the variant, which would explain the trend towards a dose-dependent efficacy of the CBZ treatment in patients with different genotypes. A larger prospective study is warranted to clarify the clinical utility of a genotype-specific individualized CBZ therapy.Keywords: multidrug resistance protein 1 (MDR1), ABCB1 C3435T polymorphism, epilepsy treatment, carbamazepineSterjev ZTrencevska GKCvetkovska EPetrov IKuzmanovski IRibarska JTNestorovska AKMatevska NNaumovska ZJolevska-Trajkovic SDimovski ASuturkova LDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2012, Iss default, Pp 191-196 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
| spellingShingle |
Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Sterjev Z Trencevska GK Cvetkovska E Petrov I Kuzmanovski I Ribarska JT Nestorovska AK Matevska N Naumovska Z Jolevska-Trajkovic S Dimovski A Suturkova L The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy |
| description |
Zoran Sterjev1, Gordana Kiteva Trencevska2, Emilija Cvetkovska2, Igor Petrov2, Igor Kuzmanovski2, Jasmina T Ribarska3, Aleksandra K Nestorovska1, Nadica Matevska1, Zorica Naumovska1, Suzana Jolevska-Trajkovic3, Aleksandar Dimovski1, Ljubica Suturkova11Institute of Pharmaceutical Chemistry, Faculty of Pharmacy Skopje, Republic of Macedonia; 2Clinic of Neurology, Faculty of Medicine, Skopje, Republic of Macedonia; 3Institute of Pharmaceutical Analysis, Faculty of Pharmacy Skopje, Republic of MacedoniaAbstract: The ABCB1 gene encodes the P-glycoprotein (Pgp) protein, which is thought to transport various antiepileptic drugs. The single nucleotide polymorphism (SNP) (C3435T) in exon 26 of this gene correlates with the altered expression levels of P-glycoprotein, range of drug response and clinical conditions. In order to investigate the influence of this polymorphism on the susceptibility to and efficacy of carbamazepine therapy, we evaluated the allelic frequency and genotype distribution of this variant in 162 epilepsy patients from the Republic of Macedonia. Statistically significant differences were detected neither in the allelic frequency and genotype distribution between carbamazepine-resistant and carbamazepine-responsive epilepsy patients nor between the subgroups of carbamazepine (CBZ)-responsive patients treated with different CBZ doses. However, the T-allele was enriched in CBZ-responsive patients who required higher maintenance CBZ doses, This observation was substantiated by the findings that the median total plasma levels were the lowest in patients with CC (20 µmol/L) followed by CT (23 µmol/L) and TT (29 µmol/L) genotypes. Patients with a CC genotype also had a higher likelihood of response compared to patients with CT or TT genotypes over a wide range (400–1000 mg/day) of initial doses of CBZ. The T allele showed a reduced expression of ~5% compared to the C allele in peripheral blood mononuclear cells in heterozygotes for the variant. This difference might be translated into ~10% difference in homozygotes for the variant, which would explain the trend towards a dose-dependent efficacy of the CBZ treatment in patients with different genotypes. A larger prospective study is warranted to clarify the clinical utility of a genotype-specific individualized CBZ therapy.Keywords: multidrug resistance protein 1 (MDR1), ABCB1 C3435T polymorphism, epilepsy treatment, carbamazepine |
| format |
article |
| author |
Sterjev Z Trencevska GK Cvetkovska E Petrov I Kuzmanovski I Ribarska JT Nestorovska AK Matevska N Naumovska Z Jolevska-Trajkovic S Dimovski A Suturkova L |
| author_facet |
Sterjev Z Trencevska GK Cvetkovska E Petrov I Kuzmanovski I Ribarska JT Nestorovska AK Matevska N Naumovska Z Jolevska-Trajkovic S Dimovski A Suturkova L |
| author_sort |
Sterjev Z |
| title |
The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy |
| title_short |
The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy |
| title_full |
The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy |
| title_fullStr |
The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy |
| title_full_unstemmed |
The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy |
| title_sort |
association of c3435t single-nucleotide polymorphism, pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy |
| publisher |
Dove Medical Press |
| publishDate |
2012 |
| url |
https://doaj.org/article/6ba46e269dde456294c428af6f671628 |
| work_keys_str_mv |
AT sterjevz theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT trencevskagk theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT cvetkovskae theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT petrovi theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT kuzmanovskii theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT ribarskajt theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT nestorovskaak theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT matevskan theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT naumovskaz theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT jolevskatrajkovics theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT dimovskia theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT suturkoval theassociationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT sterjevz associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT trencevskagk associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT cvetkovskae associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT petrovi associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT kuzmanovskii associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT ribarskajt associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT nestorovskaak associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT matevskan associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT naumovskaz associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT jolevskatrajkovics associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT dimovskia associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy AT suturkoval associationofc3435tsinglenucleotidepolymorphismpgpglycoproteingeneexpressionlevelsandcarbamazepinemaintenancedoseinpatientswithepilepsy |
| _version_ |
1718401010951520256 |