PMID- 35559956
OWN - NLM
STAT- MEDLINE
DCOM- 20220519
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 17
IP  - 5
DP  - 2022
TI  - Lack of impact of OCTN1 gene polymorphisms on clinical outcomes of gabapentinoids 
      in Pakistani patients with neuropathic pain.
PG  - e0266559
LID - 10.1371/journal.pone.0266559 [doi]
LID - e0266559
AB  - BACKGROUND AND OBJECTIVE: Gabapentinoids are the first-line drugs for neuropathic 
      pain. These drugs are the substrate of organic cation transporter (OCTN1) for 
      renal excretion and absorption across the intestinal epithelium. Gabapentinoids 
      exhibit wide interindividual variability in daily dosage and therapeutic efficacy 
      which makes titration regimens prolonged for optimal efficacy. The present study 
      aimed to investigate the possible influence of the single nucleotide polymorphism 
      (SNP) of OCTN1 on therapeutic efficacy and safety of gabapentinoids in 
      neuropathic pain patients of the Pakistani population. METHODS: Four hundred and 
      twenty-six patients were enrolled in the study. All participants were genotyped 
      for OCTN1 rs1050152 and rs3792876 by PCR-RFLP method and followed up for eight 
      weeks. The therapeutic outcomes of gabapentinoids, reduction in pain score, 
      inadequate or complete lack of response, adverse events (AEs) in responders and 
      discontinuation of treatment on account of AEs were recorded for all patients. 
      RESULTS: There was no significant association of genotypes and alleles of both 
      SNPs on the clinical response of gabapentinoids (P > 0.05). Similarly, 
      significant differences were not found in the reduction of pain scores and AEs 
      among different genotypes in the responders. The present study has reported the 
      association of OCTN1 rs1050152 and rs3792876 polymorphisms with clinical outcomes 
      of gabapentinoids for the first time in the real-world clinical setting. 
      CONCLUSION: Our results suggest a lack of influence of OCTN1 genetic variants in 
      the determination of clinical response to gabapentinoids in patients with 
      neuropathic pain in the Pakistani population. These findings signify the role of 
      renal functions in predicting the interindividual variability to therapeutic 
      responsiveness of gabapentinoids.
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 & 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 - Saleem, Salman Ahmad
AU  - Saleem SA
AD  - Department of Pain Clinic, Shifa International Hospital, Islamabad, Pakistan.
FAU - Khan, Moosa
AU  - Khan M
AD  - Department of Pharmacology & Therapeutics, Shaheed Zulfiqar Ali Bhutto Medical 
      University, Islamabad, Pakistan.
FAU - Hasan, Syed Saud
AU  - Hasan SS
AD  - Department of Pharmacology & Therapeutics, Dow Medical College, Dow University of 
      Health Sciences, Karachi, Pakistan.
FAU - Liaquat, Afrose
AU  - Liaquat A
AUID- ORCID: 0000-0001-6410-6953
AD  - Department of Biochemistry, Shifa College of Medicine, Shifa Tameer-e-Millat 
      University, Islamabad, Pakistan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220513
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Organic Cation Transport Proteins)
RN  - 0 (SLC22A4 protein, human)
RN  - 0 (Symporters)
SB  - IM
MH  - Asian People
MH  - Humans
MH  - *Neuralgia/drug therapy/genetics
MH  - *Organic Cation Transport Proteins/genetics
MH  - Pakistan
MH  - Polymorphism, Restriction Fragment Length
MH  - Polymorphism, Single Nucleotide
MH  - *Symporters/genetics
PMC - PMC9106170
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/05/14 06:00
MHDA- 2022/05/20 06:00
PMCR- 2022/05/13
CRDT- 2022/05/13 18:44
PHST- 2021/10/11 00:00 [received]
PHST- 2022/03/22 00:00 [accepted]
PHST- 2022/05/13 18:44 [entrez]
PHST- 2022/05/14 06:00 [pubmed]
PHST- 2022/05/20 06:00 [medline]
PHST- 2022/05/13 00:00 [pmc-release]
AID - PONE-D-21-32641 [pii]
AID - 10.1371/journal.pone.0266559 [doi]
PST - epublish
SO  - PLoS One. 2022 May 13;17(5):e0266559. doi: 10.1371/journal.pone.0266559. 
      eCollection 2022.