Linked Life Data

11181494

Source:http://linkedlifedata.com/resource/pubmed/id/11181494

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-2-22
pubmed:databankReference
pubmed:abstractText
Human cytochrome P450 3A4 is a major P450 enzyme in the liver and gastrointestinal tract. It plays important roles in the metabolism of a wide variety of drugs, some endogenous steroids, and harmful environmental contaminants. CYP3A4 exhibits a remarkable interindividual activity variation as high as 20-fold. To investigate whether the interindividual variation in CYP3A4 levels can be partly explained by genetic polymorphism, we analyzed DNA samples from 102 Chinese subjects by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis for novel point mutation in the CYP3A4 coding sequence and promoter region. Using PCR and directed sequencing method to establish the complete intron sequence of CYP3A4 from leukocytes, the complete genomic sequence from exon 1 through 13 of CYP3A4 was determined and published in the GenBank database (accession no. AF209389). CYP3A4-specific primers were designed accordingly. After PCR-single-strand conformation polymorphism and restriction fragment length polymorphism screening, we found three novel mutations; two are point mutations and one is insertion. The first variant allele (CYP3A4*4), an Ile118Val change, was found in 3 of 102 Chinese subjects. The next allele (CYP3A4*5), which causes a Pro218Arg amino acid change, was found in 2 of 102 subjects. We found an insertion in A(17776), designated as CYP3A4*6, which causes frame shift and an early stop codon in exon 9, in one heterozygous subject. We also investigated the CYP3A4 activity in these mutant subjects by measuring the morning spot urinary 6beta-hydroxycortisol to free cortisol ratio with the enzyme-linked immunosorbent assay method. When compared with healthy Chinese population data, the 6beta-hydroxycortisol to free cortisol ratio data suggested that these alleles (CYP3A4*4, CYP3A4*5, and CYP3A4*6) may decrease the CYP3A4 activity. Incidences of these mutations in Chinese subjects are rare. The prevalence of these point mutations in other ethnic groups and its effect on the metabolic activity of CYP3A4 remain to be further evaluated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
268-73
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11181494-Alleles, pubmed-meshheading:11181494-Asian Continental Ancestry Group, pubmed-meshheading:11181494-China, pubmed-meshheading:11181494-Cytochrome P-450 CYP3A, pubmed-meshheading:11181494-Cytochrome P-450 Enzyme System, pubmed-meshheading:11181494-DNA Mutational Analysis, pubmed-meshheading:11181494-DNA Primers, pubmed-meshheading:11181494-Exons, pubmed-meshheading:11181494-Humans, pubmed-meshheading:11181494-Hydrocortisone, pubmed-meshheading:11181494-Leukocytes, pubmed-meshheading:11181494-Mixed Function Oxygenases, pubmed-meshheading:11181494-Molecular Sequence Data, pubmed-meshheading:11181494-Point Mutation, pubmed-meshheading:11181494-Polymerase Chain Reaction, pubmed-meshheading:11181494-Polymorphism, Restriction Fragment Length, pubmed-meshheading:11181494-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:11181494-Promoter Regions, Genetic, pubmed-meshheading:11181494-Taiwan
pubmed:year
2001
pubmed:articleTitle
Novel mutations of CYP3A4 in Chinese.
pubmed:affiliation
Department of Pharmacology, National Cheng Kung University, Medical College, 1 University Road, Tainan 70101, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't