Evidence map›Paper›PMID 26555147›Full record

ArticlePloS one2015

Polymorphic Variants of SCN1A and EPHX1 Influence Plasma Carbamazepine Concentration, Metabolism and Pharmacoresistance in a Population of Kosovar Albanian Epileptic Patients.

Armond Daci, Giangiacomo Beretta, Driton Vllasaliu, Aida Shala, Valbona Govori, Giuseppe Danilo Norata, Shaip Krasniqi

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 5 pooled it
6.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 5 syntheses or guidelines pooled it, 49 citations in OpenAlex.

  1. Pooled it
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  4. Association BetweenFrontiers in neurology · 2020
    Pooled it
  5. Association between two SCN1A polymorphisms and resistance to sodium channel blocking AEDs: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 3 countries.

Armond DaciDepartment of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
Giangiacomo BerettaDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, Milan, Italy.
Driton VllasaliuUniversity of Lincoln, School of Pharmacy, Joseph Banks Laboratories, Green Lane, Lincoln, LN6 7DL, United Kingdom.
Aida ShalaDepartment of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
Valbona GovoriNeurology Clinic, University Clinical Center of Kosova, Prishtina, Kosovo.
Giuseppe Danilo NorataDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Shaip KrasniqiInstitute of Pharmacology and Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
University of Prishtina · XKOspedale Bassini · ITUniversity Clinical Center of Kosovo · XKUniversity of Lincoln · GBUniversity of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimThe present study aimed to evaluate the effects of gene variants in key genes influencing pharmacokinetic and pharmacodynamic of carbamazepine (CBZ) on the response in patients with epilepsy. MATERIALS &

methodsFive SNPs in two candidate genes influencing CBZ transport and metabolism, namely ABCB1 or EPHX1, and CBZ response SCN1A (sodium channel) were genotyped in 145 epileptic patients treated with CBZ as monotherapy and 100 age and sex matched healthy controls. Plasma concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC-UV-DAD and adjusted for CBZ dosage/kg of body weight.

resultsThe presence of the SCN1A IVS5-91G>A variant allele is associated with increased epilepsy susceptibility. Furthermore, carriers of the SCN1A IVS5-91G>A variant or of EPHX1 c.337T>C variant presented significantly lower levels of plasma CBZ compared to carriers of the common alleles (0.71 ± 0.28 vs 1.11±0.69 μg/mL per mg/Kg for SCN1A IVS5-91 AA vs GG and 0.76 ± 0.16 vs 0.94 ± 0.49 μg/mL per mg/Kg for EPHX1 c.337 CC vs TT; P<0.05 for both). Carriers of the EPHX1 c.416A>G showed a reduced microsomal epoxide hydrolase activity as reflected by a significantly decreased ratio of CBZD to CBZ (0.13 ± 0.08 to 0.26 ± 0.17, p<0.05) also of CBZD to CBZE (1.74 ± 1.06 to 3.08 ± 2.90; P<0.05) and CDRCBZD (0.13 ± 0.08 vs 0.24 ± 0.19 μg/mL per mg/Kg; P<0.05). ABCB1 3455C>T SNP and SCN1A 3148A>G variants were not associated with significant changes in CBZ pharmacokinetic. Patients resistant to CBZ treatment showed increased dosage of CBZ (657 ± 285 vs 489 ± 231 mg/day; P<0.001) but also increased plasma levels of CBZ (9.84 ± 4.37 vs 7.41 ± 3.43 μg/mL; P<0.001) compared to patients responsive to CBZ treatment. CBZ resistance was not related to any of the SNPs investigated.

conclusionsThe SCN1A IVS5-91G>A SNP is associated with susceptibility to epilepsy. SNPs in EPHX1 gene are influencing CBZ metabolism and disposition. CBZ plasma levels are not an indicator of resistance to the therapy.

Indexed as

Polymorphism, Single NucleotideAdolescentAdultAlbaniaAnticonvulsantsCarbamazepineChromatography, High Pressure LiquidEpilepsyEpoxide HydrolasesEthnicityFemaleHumansMaleMiddle AgedNAV1.1 Voltage-Gated Sodium ChannelSpectrophotometry, UltravioletAnticonvulsantsCarbamazepineEPHX1 protein, humanEpoxide HydrolasesNAV1.1 Voltage-Gated Sodium ChannelSCN1A protein, human

Identifiers

PMID26555147
PMCPMC4640545
OpenAlexW2149831801

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.