Kaori Narahara

Allele and genotype frequencies of CYP2B6 and CYP3A5 in the Japanese population.

HeadingAbstractObjective. The goal of this study was to determine the frequencies of allelic variants of CYP2B6 and CYP3A5 in the Japanese population.Methods. Genotyping of CYP2B6(*2, *3, *4, *5, *6, and *7) and CYP3A5 (*2, *3, *4, *5, and *6) was carried out in 265 unrelated Japanese subjects by polymerase chain reaction (PCR), restriction fragment length polymorphism and allele-specific, real-time PCR assays.Results. Allele frequencies for CYP2B6*2, *3, *4, *5, *6, and *7 in 256 Japanese subjects were 0.047, 0, 0.093, 0.011, 0.164, and 0, respectively. Ethnic variation in allele frequencies relative to that in Caucasian subjects was observed for CYP2B6*4 (0.093 vs 0.040), *5 (0.011 vs 0.109), *6 (0.164 vs 0.256), and *7 (0 vs 0.030). Allele frequencies for CYP3A5*2, *3, *4, *5, and *6 in 265 Japanese subjects were 0, 0.740, 0, 0.004, and 0, respectively. The frequency of the CYP3A5*1 allele is 2.8 times higher in Japanese than in Caucasians.Conclusions. Our results contribute to a better understanding of the molecular basis of ethnic differences in drug response, which may help to improve individualization of drug therapy and offer a preliminary basis for more rational use of drugs that are substrates for CYP2B6 and CYP3A5 in the Japanese population.

A simultaneous LightCycler detection assay for five genetic polymorphisms influencing drug sensitivity.

OBJECTIVES The routine detection of polymorphisms affecting drug sensitivity in patients before treatment is important in the identification of drug responders or nonresponders, and patients at increased risk of drug toxicity. Here, we present an assay for the simultaneous and rapid genotyping of five polymorphisms influencing drug sensitivity. DESIGN AND METHODS We used a hybridization probe assay on the LightCycler to detect five single nucleotide polymorphisms (SNPs): INPP1 (973C>A), ADRB2 (R16G and Q27E), HTR2A (102T>C), and mtDNA (1555A>G). Two fluorescent labeled hybridization probes were designed for the simultaneous detection of the five SNPs and detection of the variant alleles was performed by melting curve analysis. RESULTS All five SNPs were detected with a single thermocycle protocol within 40 min. The genotypes determined in this assay were identical to those obtained with conventional PCR and restriction fragment length polymorphism analysis. CONCLUSIONS To our knowledge, we report here for the first time a method for simultaneous detection of five SNPs, on a single thermocycle protocol by the LightCycler. This method is rapid, highly sensitive, and high-throughput, and is thus suitable for routine clinical use and large-scale epidemiologic studies.

Allele and genotype frequencies of polymorphic DCP1, CETP, ADRB2, and HTR2A in the Egyptian population

Abstract.Objective: The goal of this study was to determine the frequencies of important allelic variants of two drug targets, dipeptidyl carboxypeptidase (DCP1) and cholesteryl ester transfer protein (CETP), and two other drug receptors, beta-2 adrenergic receptor (ADRB2) and 5-hydroxy tryptamine 2A receptor (HTR2A), in the Egyptian population and compare them with the frequencies in other ethnic populations. Methods: A sensitive real-time polymerase chain reaction assay was developed and successfully applied for genotyping of the consensus (wild-type) alleles plus five variants of four genes: DCP1 [the insertion allele (I) versus the deletion allele (D)], CETP*TaqI (B1 versus B2), ADRB2*R16G, ADRB2*Q27E, and HTR2A*102T>C. This study was carried out in 242 unrelated Egyptian subjects and is the first to describe these allelic variants in the Egyptian population. Results: The frequencies of the tested alleles were found as: DCP1 (I:D, 0.32:0.68), CETPTaqI (B1:B2, 0.65:0.35), ADRB2*R16G (Arg16:Gly16, 0.57:0.43), ADRB2*Q27E (Gln27:Glu27, 0.76:0.24), and HTR2A*102T>C (T102:C102, 0.53:0.47). The common Arabian ancestors of the Egyptians, Spanish, Saudi, and Emirate had created a common pattern of distribution of some allelic variants (DCP1 and CETP). However, in the genotyping of ADRB2, the frequency of the polymorphism at codon 16 was found to be similar to the Chinese population, whereas that at codon 27 was similar to African-Americans with significant differences than other Caucasian populations. The frequency of the HTR2A*102T>C variant appeared to be similar to many Caucasian populations and African-Americans. Conclusions: We have explored the frequencies of important allelic variants DCP1, CETP, ADRB2, and HTR2A among the Egyptian population focusing on the ethnic diversity in the distribution of the tested mutant alleles. Our results may help in better understanding the observed ethnic variation in angiotensin-converting enzyme inhibition and atherosclerosis therapy. It also may contribute to better characterization of interethnic differences in isoprenaline and clozapine response, which will have implications for the cost effective and rational prescribing of these drugs.