Identification of a novel variant CYP2C9 allele in Chinese

Abstract

This study suggests that this novel CYP2C9 allele was correlated with reduced plasma clearance of drugs that are substrates for CYP2C9.

In Vitro and In Vivo Characterization of 13 CYP2C9 Allelic Variants Found in Chinese Han Population

“…In our study, concentrations of 4-hydroxytolbutamide of the CYP2C9*3/*3 and CYP2C9*3/*13 subjects were lower than those of the CYP2C9*1/*1, CYP2C9*1/*3, and CYP2C9*1/*13 subjects. Si et al (2004) reported that one individual with the genotype of CYP2C9*3/*13 had a 108-hour t 1/2 of tolbutamide, which was much longer than that (t 1/2 of 56.9 hours) discovered in our study. We believe that the longer monitoring time of drug concentration in our present study makes our result more precise than the previous report.…”

“…8, 0.11, 0.09, and 0.94, 0.04, 0.02 (Scordo et al, 2001), respectively. CYP2C9*13 was first discovered in Chinese Han population by Si et al (2004) and was reported to have a frequency of 0.02% in Chinese. Thereafter, a series of investigations into the catalytic activity of CYP2C9*13 in vivo and in vitro were subsequently performed using tolbutamide, diclofenac, and lornoxicam as the probing substrates (Guo et al, 2005a(Guo et al, , 2005b.…”

Functional Characterization of Novel Allelic Variants of CYP2C9 Recently Discovered in Southeast Asians

“…Recently, there has been a report of an individual heterozygous for CYP2C9*3 and a novel CYP2C9 allele, CYP2C9*13 (L90P), in an Asian population. The latter was suggested to contribute to the PM phenotype (Si et al, 2004).…”

Pyrosequencing Method for Genotyping Cytochrome P450 CYP2C8 and CYP2C9 Enzymes

“…The CYP2C9*8, *11, and *12 alleles have altered in vitro metabolic activities compared with the wild-type allele, CYP2C9*1 (10 ). Finally, CYP2C9*13 was identified in a Chinese population with an allele frequency of 0.01 and was associated with decreased CYP2C9 activity (11 ).…”

“…A larger sample of these populations would be required to identify individuals carrying these alleles. Additionally, with the recent discovery of other CYP2C9 allelic variants (10,11 ), adaptations of this method could allow detection of these variants.…”