Abstract 13578: 1-acyl-sn-glycero-3-phosphocholine Levels are Related to Obesity and Several Markers of Subclinical CV Disease and its Biosynthesis is Associated With Genetic Variants in the 9p21 Region
Background and objectives: Using a non-targeted metabolomics approach, we previously identified a strong inverse association between 1-Acyl-sn-glycero-3-phosphocholine (18:1 LysoPC) and high-sensitivity C-reactive protein (hsCRP). In this study, we further explored the association between 18:1 LysoPC and markers of inflammation, oxidative stress, clinical and subclinical markers of cardiovascular diseases. Moreover, we performed a GWAS of phosphatidylcholine/18:1 LysoPC ratio to identify genetic variants influencing 18:1 LysoPC biosynthesis.
Methods: At age 70, 1016 individuals (50% women) were investigated in the PIVUS study. Several different measurements of endothelial reactivity and arterial compliance, carotid artery ultrasonography and echocardiography were performed and seven markers of coagulation/fibrinolysis were measured. In addition, 28 markers of inflammation and oxidative stress were evaluated. Ultra performance liquid-chromatography-coupled mass spectrometry was used to perform non-targeted metabolomics. Phosphatidylcholine and 18:1 LysoPC were annotated through spectra matching with commercial standards or public databases. Participants were genotyped with Illumina OmniExpress and imputed using the 1000 Genomes March 2012 reference panel.
Results: 18:1 LysoPC was inversely related to obesity and obesity-related risk factors, but positively related with LDL-cholesterol when adjusted for CRP. It was furthermore positively related to IL-6 and MCP-1 (p<0.005) and negatively related with the ox/redox glutathione ratio (p<0.0001). 18:1 LysoPC was inversely related to several markers of subclinical cardiovascular disease, such as left ventricular mass, endothelial dysfunction, tPA and PAI-1 when adjusted for CRP, but only the inverse relationship with PAI-1 was still significant following adjustment for body mass index (p<0.002). Several SNPs in the 9p21 region, close to the INFE1 gene were genome-wide significantly associated with Phosphatidylcholine/18:1 LysoPC ratio.
Conclusions: 18:1 LysoPC was inversely related with obesity and several cardiovascular traits independently of CRP levels. Genetic variants in the 9p21 region close to INFE1 were associated with 18:1 LysoPC biosynthesis.
- © 2013 by American Heart Association, Inc.