Linked Life Data

16344723

Source:http://linkedlifedata.com/resource/pubmed/id/16344723

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-12-13
pubmed:abstractText
Cytochrome P450 3A enzymes (CYP3A) play a major role in the metabolism of steroid hormones, drugs and other chemicals, including many carcinogens. The individually variable CYP3A expression, which remains mostly unexplained, has been suggested to affect clinical phenotypes. We investigated the CYP3A locus in five ethnic groups. The degree of linkage disequilibrium (LD) differed among ethnic groups, but the most common alleles of the conserved LD regions were remarkably similar. Non-African haplotypes are few; for example, only four haplotypes account for 80% of common European Caucasian alleles. Large LD blocks of high frequencies were suggestive of selection. Accordingly, European Caucasian and Asian cohorts each contained a block of single nucleotide polymorphism (SNPs) with very high P excess values. The overlap between these blocks in these two groups contained only two of the investigated 26 SNPs and one of them was the CYP3A4*1B allele. The region centromeric of CYP3A4*1B exhibited high haplotype homozygosity in European Caucasians as opposed to African-Americans. CYP3A4*1B showed a moderate effect on CYP3A4 mRNA and protein expression, as well as on CYP3A activity assessed as Vmax of testosterone 6beta-hydroxylation in a liver bank. Our data are consistent with a functional relevance of CYP3A4*1B and with selection against this allele in non-African populations. The elimination of CYP3A4*1B involved different parts of the CYP3A locus in European Caucasians and Asians. Because CYP3A4 is involved in the vitamin D metabolism, rickets may have been the underlying selecting factor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1744-6872
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
59-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Genetic signature consistent with selection against the CYP3A4*1B allele in non-African populations.
pubmed:affiliation
Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't