title: Mutation-sensitive molecular switch method to detect CES1A2 mutation in the Chinese Han and Yao populations.
abstract: Carboxylesterase 1 (CES1) is involved in the metabolic activation of a variety of prodrugs into active derivatives and plays an important role in pharmacokinetics and pharmacodynamics. A single-nucleotide polymorphism, A(-816)C, of the CES1A2 gene has been shown to enhance transcription efficiency and increase enzyme activity. The aim of this study was to develop an easy method to detect this polymorphism. For this we used the mutation-sensitive molecular switch method to investigate the polymorphism distribution in the Chinese Han and Yao populations. The method was well validated by direct sequencing. In 204 Han individuals, the percentages of the distribution of CES1A2 A(-816)C genotypes are AA 58.33% (n=119), AC 35.78% (n=73), and CC 5.88% (n=12). The genotype frequencies are AA 47.76% (n=96), AC 42.79% (n=86), and CC 9.45% (n=19) in 201 Yaos. The frequency of the mutant C allele in the Yao population is significantly higher than that in the Han population (30.85% vs. 23.77%, p=0.0239). The method can be easily used for the detection of the single-nucleotide polymorphism in CES1A2, and we found that there is a marked difference in mutant C allele between Chinese Han and Yao populations, suggesting individual and ethnic differences of CES1 drug metabolism between these two populations.
authors.affiliation: Clinical Pharmacology Research Laboratory, The First Affiliated of Soochow University, Suzhou, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Ding
authors.forename: Yang-Lin
authors.initials: YL
authors.lastname: Deng
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Miao
mesh_terms: D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D001483:Base Sequence; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D005006:Ethnicity / Q000235:genetics / Q000706:statistics & numerical data; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000208:ethnology / Q000235:genetics; D020125:Mutation, Missense / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012680:Sensitivity and Specificity
chemical_list: C121305:CES1P1 protein, human; D002265:Carboxylic Ester Hydrolases