Sequencing of Lp-PLA2-encoding PLA2G7 gene in 2000 Europeans reveals several rare loss-of-function mutations.
Details
State: Public
Version: Final published version
Serval ID
serval:BIB_EDA8E65E6D24
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sequencing of Lp-PLA2-encoding PLA2G7 gene in 2000 Europeans reveals several rare loss-of-function mutations.
Journal
Pharmacogenomics Journal
ISSN
1473-1150 (Electronic)
ISSN-L
1470-269X
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
12
Number
5
Pages
425-431
Language
english
Notes
Publication types: Journal Article
Abstract
Elevated plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA2) activity have been shown to be associated with increased risk of coronary heart disease and an inhibitor of this enzyme is under development for the treatment of that condition. A Val279Phe null allele in this gene, that may influence patient eligibility for treatment, is relatively common in East Asians but has not been observed in Europeans. We investigated the existence and functional effects of low frequency alleles in a Western European population by re-sequencing the exons of PLA2G7 in 2000 samples. In all, 19 non-synonymous single-nucleotide polymorphisms (nsSNPs) were found, 14 in fewer than four subjects (minor allele frequency <0.1%). Lp-PLA2 activity was significantly lower in rare nsSNP carriers compared with non-carriers (167.8±63.2 vs 204.6±41.8, P=0.01) and seven variants had enzyme activities consistent with a null allele. The cumulative frequency of these null alleles was 0.25%, so <1 in 10,000 Europeans would be expected to be homozygous, and thus not potentially benefit from treatment with an Lp-PLA2 inhibitor.
Pubmed
Web of science
Open Access
Yes
Create date
10/01/2013 12:23
Last modification date
20/08/2019 17:15