title: Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease.
abstract: 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.
authors.affiliation: INSERM, UMRS937, UPMC Université Paris 06 and Faculté de Médecine Pierre et Marie Curie, 91, Boulevard de l'Hôpital, 75634, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gora
authors.forename: Claire
authors.initials: C
authors.lastname: Perret
authors.forename: Ikram
authors.initials: I
authors.lastname: Jemel
authors.forename: Viviane
authors.initials: V
authors.lastname: Nicaud
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Ewa
authors.initials: E
authors.lastname: Ninio
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Sonia-Athina
authors.initials: SA
authors.lastname: Karabina
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D015200:Fluoroimmunoassay; D020022:Genetic Predisposition to Disease / Q000235:genetics; D054509:Group X Phospholipases A2 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D054509:Group X Phospholipases A2