PMID- 33190395
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20211004
IS  - 1742-7843 (Electronic)
IS  - 1742-7835 (Linking)
VI  - 128
IP  - 3
DP  - 2021 Mar
TI  - Influence of single nucleotide polymorphism of LAT1 on therapeutic response to 
      gabapentinoids in Pakistani patients with neuropathic pain.
PG  - 503-510
LID - 10.1111/bcpt.13534 [doi]
AB  - Gabapentinoids are substrate of L-type amino acid transporter 1 (LAT1) for 
      distribution across the blood-brain barrier. The present study aimed to evaluate 
      the effect of LAT1 rs4240803 genetic polymorphism on the clinical efficacy and 
      tolerability of gabapentinoids in Pakistani patients with neuropathic pain. 
      Three-hundred and ninety-two patients were recruited, genotyped for SNP 
      rs4240803, and followed up for eight weeks to evaluate the clinical response to 
      gabapentinoids in terms of pain relief, inadequate response, and the emergence of 
      adverse events. LAT1 rs4240803 GG, GA, and AA genotype frequency were 33.42%, 
      47.96% and 18.62%, respectively. Out of 392 patients, 323 responded to the 
      treatment and 17.6% discontinued either due to insufficient response or 
      intolerable adverse events (AEs). GA genotype was more frequent in non-responder 
      group (P < 0.001). Maximum pain responders (>/=50%) in combination with the lowest 
      incidence of AEs were observed in the GG group, whereas partial responders 
      belonged to GA genotype and with the highest frequency of somnolence (83.6%) and 
      dizziness (69.9%). Overall, 72.5% patients with GA genotype experienced AEs 
      (P < 0.001). In conclusion, clinical outcomes of gabapentinoids are influenced by 
      LAT1 rs4240803 polymorphism and population pharmacogenetics should be considered 
      to evaluate the maximum potential of gabapentinoids in the management of 
      neuropathic pain.
CI  - (c) 2020 Nordic Association for the Publication of BCPT (former Nordic 
      Pharmacological Society).
FAU - Shaheen, Abida
AU  - Shaheen A
AUID- ORCID: 0000-0001-8977-9820
AD  - Department of Pharmacology & Therapeutics, Shifa College of Medicine, Shifa 
      Tameer-e-Millat University, Islamabad, Pakistan.
FAU - Alam, Syed Mahboob
AU  - Alam SM
AD  - Department of Pharmacology and Therapeutics, Basic Medical Sciences Institute, 
      JPMC, Karachi, Pakistan.
FAU - Azam, Fahad
AU  - Azam F
AD  - Department of Pharmacology & Therapeutics, Shifa College of Medicine, Shifa 
      Tameer-e-Millat University, Islamabad, Pakistan.
FAU - Khan, Moosa
AU  - Khan M
AD  - Department of Pharmacology & Therapeutics, Shaheed Zulfiqar Ali Bhutto Medical 
      University, Islamabad, Pakistan.
FAU - Ahmad Saleem, Salman
AU  - Ahmad Saleem S
AD  - Department of Pain Clinic, Shifa International Hospital, Islamabad, Pakistan.
FAU - Liaquat, Afrose
AU  - Liaquat A
AD  - Department of Biochemistry, Shifa College of Medicine, Shifa Tameer-e-Millat 
      University, Islamabad, Pakistan.
FAU - Mumtaz, Sana
AU  - Mumtaz S
AD  - Department of Psychosomatic Medicine and Psychotherapy, University Medical Center 
      Gӧttingen, Gӧttingen, Germany.
LA  - eng
GR  - Shifa Tameer-e-Millat University, Islamabad, Pakistan/
PT  - Journal Article
DEP - 20201212
PL  - England
TA  - Basic Clin Pharmacol Toxicol
JT  - Basic & clinical pharmacology & toxicology
JID - 101208422
RN  - 0 (Large Neutral Amino Acid-Transporter 1)
RN  - 0 (SLC7A5 protein, human)
RN  - 6CW7F3G59X (Gabapentin)
SB  - IM
MH  - Adult
MH  - Female
MH  - Gabapentin/adverse effects/*therapeutic use
MH  - Genotype
MH  - Humans
MH  - Large Neutral Amino Acid-Transporter 1/*genetics
MH  - Male
MH  - Middle Aged
MH  - Neuralgia/*drug therapy/genetics
MH  - *Polymorphism, Single Nucleotide
OTO - NOTNLM
OT  - gabapentin
OT  - neuropathic pain
OT  - pharmacogenetics
OT  - polymorphism
OT  - pregabalin
EDAT- 2020/11/16 06:00
MHDA- 2021/10/05 06:00
CRDT- 2020/11/15 20:38
PHST- 2020/09/22 00:00 [received]
PHST- 2020/11/02 00:00 [revised]
PHST- 2020/11/09 00:00 [accepted]
PHST- 2020/11/16 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2020/11/15 20:38 [entrez]
AID - 10.1111/bcpt.13534 [doi]
PST - ppublish
SO  - Basic Clin Pharmacol Toxicol. 2021 Mar;128(3):503-510. doi: 10.1111/bcpt.13534. 
      Epub 2020 Dec 12.