TY - JOUR T1 - Genetic Polymorphism of Cytochrome P450 3A5 in Chinese JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1205 LP - 1209 VL - 29 IS - 9 AU - Fang-Chun Chou AU - Shwu-Jen Tzeng AU - Jin-ding Huang Y1 - 2001/09/01 UR - http://dmd.aspetjournals.org/content/29/9/1205.abstract N2 - The CYP3A subfamily enzymes are the most abundant and important drug-metabolizing enzymes. Wide variation in the CYP3A5 expression was well known. Recently, G−44 to A of CYP3AP1was found to segregate with CYP3A5*3 defective allele. The homozygous A−44 subjects showed low expression of CYP3A5. In Caucasian, only 9.2% of CYP3AP1 alleles were with G−44 and associated with the wild-type CYP3A5*1 allele, which expressed CYP3A5 significantly. By using polymerase chain reaction and FauI endonuclease digestion, we found that 28% of CYP3AP1 alleles are G−44in 110 Chinese subjects. The frequency is 3 times higher in Chinese than in Caucasian, implying more Chinese subjects are probably extensive CYP3A5 metabolizers. In two Chinese subjects, we also found a heterozygous G13048gt-to-G13048gc mutation at the intron 5 splicing donor site, leading to a splicing defect. A 6478-base pair minigene, including intron 4 to intron 7, was used for in vitro transcription. Both the wild-type and the mutated minigenes produced splicing variants. The wild-type minigene used Ggt13050 as the splicing donor. The mutant minigene used gt8504 in intron 4 or gt13112 in intron 5 as the splicing donor for various splicing acceptors. The splicing defect may result in a shorter peptide or cause the frame shift. In the other two Chinese subjects, we found A14763-to-G mutation in exon 7, resulting in the Q200R amino acid change. The consequence of the polymorphism site has not been known. In Caucasian, there is a reported T398N polymorphism. In these Chinese subjects, we did not find polymorphism at this site. The American Society for Pharmacology and Experimental Therapeutics ER -