Authors: An Wang BangNing Yu ChenHui Luo ZhiRong Tan Gan Zhou LianSheng Wang Wei Zhang Zhi Li Jie Liu HongHao Zhou
Publish Date: 2005/01/14
Volume: 60, Issue: 12, Pages: 843-848
Abstract
From hospitalized and nonhospitalized patients 211 unrelated hyperlipidemic patients were recruited for genotyping CYP3A4 genotypes were determined by means of polymerase chain reaction and restriction fragment length polymorphism analysis Of the nonhospitalized hyperlipidemic patients 8 with CYP3A41/1 and 8 with CYP3A41/4 genotypes were selected to be treated with 20 mg simvastatin daily for 4 weeks Serum triglycerides TG cholesterol CHO and lowdensity lipoprotein LDL levels were determined using an automated analyzer Hitachi 747 Boehringer Mannheim Mannheim Germany CYP3A4 activity was determined by the ratio of 6hydroxycortisol to free cortisol 6OHC/FC in the morning spot urine with a highthroughput liquid chromatography–tandem mass spectrometry methodOf 211 subjects 14 allele frequency 332 were heterozygous for CYP3A44 Ile118Val Nevertheless no subjects with a CYP3A45 or CYP3A46 allele or homozygous for CYP3A44 were identified The ratio of 6βOHC/FC was 99±137 and 566±357 in subjects with the Ile118Val variant n=8 and in CYP3A4 wildtype subjects n=8 respectively P=00039 After oral intake of simvastatin 20 mg daily for 4 weeks the change of serum lipids in CYP3A41/1 and CYP3A41/4 groups showed a significant difference with a mean decrease in triglycerides and total cholesterol of 381±76 versus 251±83 P=0034 and of 358±96 versus 220±204 P=00015 means ± SD respectively We found no statistically significant difference in the reductions of LDL between subjects carrying the 1 and 4 genotypes 290±74 versus 368±88 P=00721The allele frequency of CYP3A44 was 332 among the hyperlipidemic patients from the Chinese mainland CYP3A44 was an allelic variant related to a functional decrease of CYP3A4 activity and 4 expression seemed to increase the lipidlowering effects of simvastatin
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