Influence of genetic variations in ABCB1 on the clinical efficacy of ondansetron - A pharmacogenetic analysis of Pakistani population.
OBJECTIVE
To study the association of C1236T single-nucleotide polymorphisms of ABCB1 gene with non-responsiveness to antiemetic treatment in post-operative patients.


METHODS
The prospective, clinical trial was conducted at Combined Military Hospital, Rawalpindi, and the Institute of Biomedical and Genetic Engineering, Islamabad, in 2012-13, and comprised patients undergoing elective laparoscopic cholecystectomy. All patients were given 0.1 mg/kg ondansetron intravenously 30 minutes before the end of surgery and Deoxyribonucleic acid samples were obtained. The frequencies of genotypes of Single Nucleotide Polymorphism were determined by polymerase chain reaction followed by restriction fragment length polymorphism.


RESULTS
Of the 426 patients, 201(47%) were responders having no nausea or vomiting, and 225(52.8%) were non-responders having nausea or vomiting. The incidence of post-operative nausea and vomiting during the first 2 hours after surgery was significantly lower in patients with 1236TT genotype than other 1236 genotypes (p<0.001). It was significantly higher in patients with CC genotype at 2 hours than other 1236 genotypes (p<0.001).


CONCLUSIONS
Polymorphism of ABCB1 gene may be a good guide for predicting responsiveness for ondansetron.
Department of Pharmacology & Therapeutics, Army Medical College, (National University of Sciences and Technology), Rawalpindi.
Kulsoom
K
Farhat
Department of Pharmacology & Therapeutics, Army Medical College, (National University of Sciences and Technology), Rawalpindi.
Akbar
A
Waheed
Hamdard Institute of Pharmaceutical Sciences, Islamabad.
Azhar
A
Hussain
Institute of Biomedical and Genetic Engineering, Islamabad.
Muhammad
M
Ismail
Institute of Biomedical and Genetic Engineering, Islamabad.
Qaisar
Q
Mansoor
Department of Anesthesia, Combined Military Hospital, Rawalpindi.
Anwar Kamal
AK
Pasha
Department of Pharmacology & Therapeutics, Margalla Institute of Dentistry, Islamabad.
Nusrat
N
Jafery
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D017081:Cholecystectomy, Laparoscopic; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D017294:Ondansetron / Q000627:therapeutic use*; D010154:Pakistan; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000932:Antiemetics; D017294:Ondansetron
ATP-binding cassette subfamily B member 1 (ABCB1), Single nucleotide polymorphism, Genotyping, Ondansetron, P-glycoprotein.