Study on the CYP2C9 and CYP2C19 genetic polymorphism in Chinese subjects by using 3-dimense polyacrylamide gel-based microarray platform

Abstract

Abstract: AIM: To study the genetic polymorphisms of CYP2C9 and CYP2C19 by using 3-dimense polyacrylamide gel-based microarray method in healthy male Chinese subjects, providing original technology and research method for clinical rational administration. METHODS: 207 healthy male Chinese volunteers were recruited and their genomic DNA were isolated. The genomic fragments containing CYP2C9 ^* 3, ^* 13 and CYP2C19 ^* 2, ^* 3 polymorphic sites were amplified respectively to prepare 3-dimense polyacrylamide gel-based microarrays. After hybridized by fluorescent labeling probes, the microarrays were scanned to obtain genotyping results of CYP2C9 and CYP2C19.The analytic results were confirmed by direct sequencing. RESULTS: In 207 volunteers, the number of subjects with CYP2C9 ^* 1/^*3, CYP2C9 ^* 1/^* 13 and CYP2C9 ^* 3/^* 3 genotype were 11, 1, and 1, respectively. The frequencies of CYP2C9 ^* 3 and CYP2C9 ^* 13 alleles were 2.90 %and 0.24 %, respectively. The incidence of CYP2C9 poor metabolizers was 0.48 %. With regard to CYP2C19, heterozygous variants were 97 and homozygous variants were 26.The frequencies of CYP2C19 ^* 2 and CYP2C19 ^* 3 alleles were 32.85 % and 3.62 %, respectively. The incidence of CYP2C19 poor metabolizers was 12.56 %.The distribution of the four alleles were all coincident with Hardy-Weinberg law. CONCLUSION: 3-dimense polyacrylamide gelbased microarray method could serve as an advanced platform for clinical genotyping. The polymorphisms of CYP2C9 and CYP2C19 are frequent in Chinese population. Detecting the Genotyping CYP2C9 and CYP2C19 gene before administration could optimize related clinical drugs therapy, with the purpose of high efficiency and low incidence of adverse reactions.

Key words: CYP2C9, CYP2C19, genetic polymorphism, 3-dimense polyacrylamide gel-based microarray, DNA purification

CLC Number:

R969

MA Jing-jing, LI Jin-heng, CHENG Lu. Study on the CYP2C9 and CYP2C19 genetic polymorphism in Chinese subjects by using 3-dimense polyacrylamide gel-based microarray platform[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(9): 966-973.

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