5 HT3-receptor antagonists and cardiac repolarization time in patients expressing a novel genetic target associated with baseline QTc interval abnormalities

Sadeq A. Quraishi, Gregg H. Schuler, Piotr Janicki

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Study Objective: To investigate whether a common single nucleotide polymorphism (SNP), rs10494366, is associated with significant prolongation of the QTc interval following administration of 5-HT3-receptor antagonists in the perioperative setting. Design: Post-hoc analysis of deoxyribonucleic acid (DNA) samples and electrocardiographic (ECG) data from an established perioperative genomics database. Setting: University teaching hospital. Measurements: DNA samples of 132 ASA physical status 1, 2, and 3 patients were obtained from an established genomic database of surgical patients who had received either granisetron or dolasetron as part of their general anesthesia plan. ECG recordings were collected on all subjects before administration of antiemetic medication, then 10 minutes after drug injection. DNA analysis was performed using TaqMan real-time PCR genotyping assay. Results from the TaqMan real-time PCR assay were used to calculate relative frequencies of the T (major) and G (minor) alleles, in addition to calculating the genotype frequencies. QTc intervals were calculated according to Bazett's formula. Results: Relative frequencies for T and G alleles were 0.63 and 0.37, respectively. The relative frequencies of the pertinent genotypes were TT 39.4%, TG 46.9%, and GG 13.7%. No significant difference was noted in QTc interval pre-antiemetic or post-antiemetic drug administration for the homozygous carriers of the minor allele GG (P = 0.059), but a significant difference was seen in the pre-drug and post-drug QTc intervals in the heterozygous and homozygous carriers of the major allele TG and TT (P = 0.003 and P = 0.017, respectively). Compared with homozygous carriers of the minor allele, absolute risk increase for QTc interval prolongation after antiemetic administration was 0.08 and 0.15 in heterozygous and homozygous carriers of the major allele, respectively. Conclusion: Homozygous and heterozygous carrier status for the major SNP, rs10494366 allele (T), in intron 1 of the human NOSA1P gene may be associated with an increased risk of QTc interval prolongation following administration of 5-HT3-receptor antagonists in the perioperative setting, when compared with homozygotes for the minor (G) allele.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalJournal of Clinical Anesthesia
Volume23
Issue number4
DOIs
StatePublished - Jun 1 2011

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Serotonin 5-HT3 Receptor Antagonists
Receptors, Serotonin, 5-HT3
Alleles
Antiemetics
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
DNA
Genotype
Pharmaceutical Preparations
Databases
Granisetron
Homozygote
Genomics
Teaching Hospitals
Introns
General Anesthesia
Injections

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

@article{d442a6c0f30c477cb6fdfc86754703f6,
title = "5 HT3-receptor antagonists and cardiac repolarization time in patients expressing a novel genetic target associated with baseline QTc interval abnormalities",
abstract = "Study Objective: To investigate whether a common single nucleotide polymorphism (SNP), rs10494366, is associated with significant prolongation of the QTc interval following administration of 5-HT3-receptor antagonists in the perioperative setting. Design: Post-hoc analysis of deoxyribonucleic acid (DNA) samples and electrocardiographic (ECG) data from an established perioperative genomics database. Setting: University teaching hospital. Measurements: DNA samples of 132 ASA physical status 1, 2, and 3 patients were obtained from an established genomic database of surgical patients who had received either granisetron or dolasetron as part of their general anesthesia plan. ECG recordings were collected on all subjects before administration of antiemetic medication, then 10 minutes after drug injection. DNA analysis was performed using TaqMan real-time PCR genotyping assay. Results from the TaqMan real-time PCR assay were used to calculate relative frequencies of the T (major) and G (minor) alleles, in addition to calculating the genotype frequencies. QTc intervals were calculated according to Bazett's formula. Results: Relative frequencies for T and G alleles were 0.63 and 0.37, respectively. The relative frequencies of the pertinent genotypes were TT 39.4{\%}, TG 46.9{\%}, and GG 13.7{\%}. No significant difference was noted in QTc interval pre-antiemetic or post-antiemetic drug administration for the homozygous carriers of the minor allele GG (P = 0.059), but a significant difference was seen in the pre-drug and post-drug QTc intervals in the heterozygous and homozygous carriers of the major allele TG and TT (P = 0.003 and P = 0.017, respectively). Compared with homozygous carriers of the minor allele, absolute risk increase for QTc interval prolongation after antiemetic administration was 0.08 and 0.15 in heterozygous and homozygous carriers of the major allele, respectively. Conclusion: Homozygous and heterozygous carrier status for the major SNP, rs10494366 allele (T), in intron 1 of the human NOSA1P gene may be associated with an increased risk of QTc interval prolongation following administration of 5-HT3-receptor antagonists in the perioperative setting, when compared with homozygotes for the minor (G) allele.",
author = "Quraishi, {Sadeq A.} and Schuler, {Gregg H.} and Piotr Janicki",
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5 HT3-receptor antagonists and cardiac repolarization time in patients expressing a novel genetic target associated with baseline QTc interval abnormalities. / Quraishi, Sadeq A.; Schuler, Gregg H.; Janicki, Piotr.

In: Journal of Clinical Anesthesia, Vol. 23, No. 4, 01.06.2011, p. 297-302.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 5 HT3-receptor antagonists and cardiac repolarization time in patients expressing a novel genetic target associated with baseline QTc interval abnormalities

AU - Quraishi, Sadeq A.

AU - Schuler, Gregg H.

AU - Janicki, Piotr

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Study Objective: To investigate whether a common single nucleotide polymorphism (SNP), rs10494366, is associated with significant prolongation of the QTc interval following administration of 5-HT3-receptor antagonists in the perioperative setting. Design: Post-hoc analysis of deoxyribonucleic acid (DNA) samples and electrocardiographic (ECG) data from an established perioperative genomics database. Setting: University teaching hospital. Measurements: DNA samples of 132 ASA physical status 1, 2, and 3 patients were obtained from an established genomic database of surgical patients who had received either granisetron or dolasetron as part of their general anesthesia plan. ECG recordings were collected on all subjects before administration of antiemetic medication, then 10 minutes after drug injection. DNA analysis was performed using TaqMan real-time PCR genotyping assay. Results from the TaqMan real-time PCR assay were used to calculate relative frequencies of the T (major) and G (minor) alleles, in addition to calculating the genotype frequencies. QTc intervals were calculated according to Bazett's formula. Results: Relative frequencies for T and G alleles were 0.63 and 0.37, respectively. The relative frequencies of the pertinent genotypes were TT 39.4%, TG 46.9%, and GG 13.7%. No significant difference was noted in QTc interval pre-antiemetic or post-antiemetic drug administration for the homozygous carriers of the minor allele GG (P = 0.059), but a significant difference was seen in the pre-drug and post-drug QTc intervals in the heterozygous and homozygous carriers of the major allele TG and TT (P = 0.003 and P = 0.017, respectively). Compared with homozygous carriers of the minor allele, absolute risk increase for QTc interval prolongation after antiemetic administration was 0.08 and 0.15 in heterozygous and homozygous carriers of the major allele, respectively. Conclusion: Homozygous and heterozygous carrier status for the major SNP, rs10494366 allele (T), in intron 1 of the human NOSA1P gene may be associated with an increased risk of QTc interval prolongation following administration of 5-HT3-receptor antagonists in the perioperative setting, when compared with homozygotes for the minor (G) allele.

AB - Study Objective: To investigate whether a common single nucleotide polymorphism (SNP), rs10494366, is associated with significant prolongation of the QTc interval following administration of 5-HT3-receptor antagonists in the perioperative setting. Design: Post-hoc analysis of deoxyribonucleic acid (DNA) samples and electrocardiographic (ECG) data from an established perioperative genomics database. Setting: University teaching hospital. Measurements: DNA samples of 132 ASA physical status 1, 2, and 3 patients were obtained from an established genomic database of surgical patients who had received either granisetron or dolasetron as part of their general anesthesia plan. ECG recordings were collected on all subjects before administration of antiemetic medication, then 10 minutes after drug injection. DNA analysis was performed using TaqMan real-time PCR genotyping assay. Results from the TaqMan real-time PCR assay were used to calculate relative frequencies of the T (major) and G (minor) alleles, in addition to calculating the genotype frequencies. QTc intervals were calculated according to Bazett's formula. Results: Relative frequencies for T and G alleles were 0.63 and 0.37, respectively. The relative frequencies of the pertinent genotypes were TT 39.4%, TG 46.9%, and GG 13.7%. No significant difference was noted in QTc interval pre-antiemetic or post-antiemetic drug administration for the homozygous carriers of the minor allele GG (P = 0.059), but a significant difference was seen in the pre-drug and post-drug QTc intervals in the heterozygous and homozygous carriers of the major allele TG and TT (P = 0.003 and P = 0.017, respectively). Compared with homozygous carriers of the minor allele, absolute risk increase for QTc interval prolongation after antiemetic administration was 0.08 and 0.15 in heterozygous and homozygous carriers of the major allele, respectively. Conclusion: Homozygous and heterozygous carrier status for the major SNP, rs10494366 allele (T), in intron 1 of the human NOSA1P gene may be associated with an increased risk of QTc interval prolongation following administration of 5-HT3-receptor antagonists in the perioperative setting, when compared with homozygotes for the minor (G) allele.

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