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Clinically relevant genetic variants of drug-metabolizing enzyme and transporter genes detected in Thai children and adolescents with autism spectrum disorder.

Medhasi S, Pasomsub E, Vanwong N, Ngamsamut N, Puangpetch A, Chamnanphon M, Hongkaew Y, Limsila P, Pinthong D, Sukasem C - Neuropsychiatr Dis Treat (2016)

Bottom Line: Thereafter, the genetic variations of significant DMET genes were assessed.Many clinically relevant SNPs, including CYP2C19*2, CYP2D6*10, CYP3A5*3, and SLCO1B1*5, were found to have frequencies similar to those in the Chinese population.These data are important for further research to investigate the interpatient variability in pharmacokinetics and pharmacodynamics of drugs in clinical practice.

View Article: PubMed Central - PubMed

Affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.

ABSTRACT
Single-nucleotide polymorphisms (SNPs) among drug-metabolizing enzymes and transporters (DMETs) influence the pharmacokinetic profile of drugs and exhibit intra- and interethnic variations in drug response in terms of efficacy and safety profile. The main objective of this study was to assess the frequency of allelic variants of drug absorption, distribution, metabolism, and elimination-related genes in Thai children and adolescents with autism spectrum disorder. Blood samples were drawn from 119 patients, and DNA was extracted. Genotyping was performed using the DMET Plus microarray platform. The allele frequencies of the DMET markers were generated using the DMET Console software. Thereafter, the genetic variations of significant DMET genes were assessed. The frequencies of SNPs across the genes coding for DMETs were determined. After filtering the SNPs, 489 of the 1,931 SNPs passed quality control. Many clinically relevant SNPs, including CYP2C19*2, CYP2D6*10, CYP3A5*3, and SLCO1B1*5, were found to have frequencies similar to those in the Chinese population. These data are important for further research to investigate the interpatient variability in pharmacokinetics and pharmacodynamics of drugs in clinical practice.

No MeSH data available.


Related in: MedlinePlus

Flow diagram of genetic marker selection.Abbreviations: DMET, drug-metabolizing enzymes and transporters; HWE, Hardy–Weinberg equilibrium; MAF, minor allele frequency; SNPs, single-nucleotide polymorphisms.
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f1-ndt-12-843: Flow diagram of genetic marker selection.Abbreviations: DMET, drug-metabolizing enzymes and transporters; HWE, Hardy–Weinberg equilibrium; MAF, minor allele frequency; SNPs, single-nucleotide polymorphisms.

Mentions: Quality control of the samples and SNPs was performed as shown in Figure 1. Individual samples were considered passed or in bounds if they had genotyping calls >90%. The markers with genotyping call rate <95%, deviation from Hardy–Weinberg equilibrium (HWE) at P>0.001, minor allele frequency (MAF) <0.05, and variants on chromosome X were discarded.


Clinically relevant genetic variants of drug-metabolizing enzyme and transporter genes detected in Thai children and adolescents with autism spectrum disorder.

Medhasi S, Pasomsub E, Vanwong N, Ngamsamut N, Puangpetch A, Chamnanphon M, Hongkaew Y, Limsila P, Pinthong D, Sukasem C - Neuropsychiatr Dis Treat (2016)

Flow diagram of genetic marker selection.Abbreviations: DMET, drug-metabolizing enzymes and transporters; HWE, Hardy–Weinberg equilibrium; MAF, minor allele frequency; SNPs, single-nucleotide polymorphisms.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835132&req=5

f1-ndt-12-843: Flow diagram of genetic marker selection.Abbreviations: DMET, drug-metabolizing enzymes and transporters; HWE, Hardy–Weinberg equilibrium; MAF, minor allele frequency; SNPs, single-nucleotide polymorphisms.
Mentions: Quality control of the samples and SNPs was performed as shown in Figure 1. Individual samples were considered passed or in bounds if they had genotyping calls >90%. The markers with genotyping call rate <95%, deviation from Hardy–Weinberg equilibrium (HWE) at P>0.001, minor allele frequency (MAF) <0.05, and variants on chromosome X were discarded.

Bottom Line: Thereafter, the genetic variations of significant DMET genes were assessed.Many clinically relevant SNPs, including CYP2C19*2, CYP2D6*10, CYP3A5*3, and SLCO1B1*5, were found to have frequencies similar to those in the Chinese population.These data are important for further research to investigate the interpatient variability in pharmacokinetics and pharmacodynamics of drugs in clinical practice.

View Article: PubMed Central - PubMed

Affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.

ABSTRACT
Single-nucleotide polymorphisms (SNPs) among drug-metabolizing enzymes and transporters (DMETs) influence the pharmacokinetic profile of drugs and exhibit intra- and interethnic variations in drug response in terms of efficacy and safety profile. The main objective of this study was to assess the frequency of allelic variants of drug absorption, distribution, metabolism, and elimination-related genes in Thai children and adolescents with autism spectrum disorder. Blood samples were drawn from 119 patients, and DNA was extracted. Genotyping was performed using the DMET Plus microarray platform. The allele frequencies of the DMET markers were generated using the DMET Console software. Thereafter, the genetic variations of significant DMET genes were assessed. The frequencies of SNPs across the genes coding for DMETs were determined. After filtering the SNPs, 489 of the 1,931 SNPs passed quality control. Many clinically relevant SNPs, including CYP2C19*2, CYP2D6*10, CYP3A5*3, and SLCO1B1*5, were found to have frequencies similar to those in the Chinese population. These data are important for further research to investigate the interpatient variability in pharmacokinetics and pharmacodynamics of drugs in clinical practice.

No MeSH data available.


Related in: MedlinePlus