Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease
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Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease. / Gora, Sarah; Perret, Claire; Jemel, Ikram; Nicaud, Viviane; Lambeau, Gérard; Cambien, François; Ninio, Ewa; Blankenberg, Stefan; Tiret, Laurence; Karabina, Sonia-Athina.
in: J MOL MED, Jahrgang 87, Nr. 7, 07.2009, S. 723-733.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease
AU - Gora, Sarah
AU - Perret, Claire
AU - Jemel, Ikram
AU - Nicaud, Viviane
AU - Lambeau, Gérard
AU - Cambien, François
AU - Ninio, Ewa
AU - Blankenberg, Stefan
AU - Tiret, Laurence
AU - Karabina, Sonia-Athina
PY - 2009/7
Y1 - 2009/7
N2 - Among secreted phospholipases A2 (sPLA2s), human group X sPLA2 (hGX sPLA2) is emerging as a novel attractive therapeutic target due to its implication in inflammatory diseases. To elucidate whether hGX sPLA2 plays a causative role in coronary artery disease (CAD), we screened the human PLA2G10 gene to identify polymorphisms and possible associations with CAD end-points in a prospective study, AtheroGene. We identified eight polymorphisms, among which, one non-synonymous polymorphism R38C in the propeptide region of the sPLA2. The T-512C polymorphism located in the 5' untranslated region was associated with a decreased risk of recurrent cardiovascular events during follow-up. The functional analysis of the R38C polymorphism showed that it leads to a profound change in expression and activity of hGX sPLA2, although there was no detectable impact on CAD risk. Due to the potential role of hGX sPLA2 in inflammatory processes, these polymorphisms should be investigated in other inflammatory diseases.
AB - Among secreted phospholipases A2 (sPLA2s), human group X sPLA2 (hGX sPLA2) is emerging as a novel attractive therapeutic target due to its implication in inflammatory diseases. To elucidate whether hGX sPLA2 plays a causative role in coronary artery disease (CAD), we screened the human PLA2G10 gene to identify polymorphisms and possible associations with CAD end-points in a prospective study, AtheroGene. We identified eight polymorphisms, among which, one non-synonymous polymorphism R38C in the propeptide region of the sPLA2. The T-512C polymorphism located in the 5' untranslated region was associated with a decreased risk of recurrent cardiovascular events during follow-up. The functional analysis of the R38C polymorphism showed that it leads to a profound change in expression and activity of hGX sPLA2, although there was no detectable impact on CAD risk. Due to the potential role of hGX sPLA2 in inflammatory processes, these polymorphisms should be investigated in other inflammatory diseases.
KW - 5' Untranslated Regions/genetics
KW - Adult
KW - Aged
KW - Coronary Artery Disease/enzymology
KW - Female
KW - Fluoroimmunoassay
KW - Genetic Predisposition to Disease/genetics
KW - Group X Phospholipases A2/genetics
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Microscopy, Confocal
KW - Middle Aged
KW - Mutagenesis, Site-Directed
KW - Polymorphism, Genetic/genetics
U2 - 10.1007/s00109-009-0483-y
DO - 10.1007/s00109-009-0483-y
M3 - SCORING: Journal article
C2 - 19495570
VL - 87
SP - 723
EP - 733
JO - J MOL MED
JF - J MOL MED
SN - 0946-2716
IS - 7
ER -