Molecular and functional characterization of polymorphisms in the secreted phospholipase A2 group X gene: relevance to coronary artery disease.
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.
Gora
Sarah
S
INSERM, UMRS937, UPMC Université Paris 06 and Faculté de Médecine Pierre et Marie Curie, 91, Boulevard de l'Hôpital, 75634, Paris, France.
Perret
Claire
C
Jemel
Ikram
I
Nicaud
Viviane
V
Lambeau
Gérard
G
Cambien
François
F
Ninio
Ewa
E
Blankenberg
Stefan
S
Tiret
Laurence
L
Karabina
Sonia-Athina
SA
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*
D020121:5' Untranslated Regions; D054509:Group X Phospholipases A2