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Molecular pathways associated with blood pressure and hexadecanedioate levels
Cristina Menni1, Sarah J Metrustry1, Georg Ehret2
1Department of Twin Research and Genetic Epidemiology, Kings College London, London, United Kingdom.
Plos One
|April 14, 2017
Summary
High levels of the dicarboxylic acid hexadecanedioate are linked to blood pressure (BP). This study identifies genetic links and molecular pathways, revealing hexadecanedioate regulates alcohol
Area of Science:
- Human Genetics
- Metabolomics
- Cardiovascular Disease Research
Background:
- The dicarboxylic acid hexadecanedioate is associated with elevated blood pressure (BP) and mortality in humans.
- Dietary administration of hexadecanedioate in rats has been shown to increase BP.
Purpose of the Study:
- To characterize the molecular pathways influencing hexadecanedioate levels in relation to BP regulation.
- To investigate genetic associations and gene expression patterns linked to hexadecanedioate.
Main Methods:
- Genome-wide association scan (GWAS) on 6447 individuals from TwinsUK and KORA cohorts to identify genetic loci associated with hexadecanedioate.
- Testing top hexadecanedioate associations for linkage with BP and hypertension in large consortia and extreme BP GWAS.
- Transcriptomic analysis correlating hexadecanedioate levels with gene expression in adipose tissue of 740 TwinsUK participants.
Main Results:
- GWAS identified 242 single nucleotide polymorphisms (SNPs) at two independent loci associated with hexadecanedioate levels.
- A significant SNP (rs414056) in the SCLO1B1 gene was associated with higher hexadecanedioate but not BP.
- The top SNP (rs6663731) mapped to CYP4Z2P; hexadecanedioate levels correlated with adipose gene expression of CYP4 and alcohol dehydrogenase (ADH) probes.
- High hexadecanedioate levels significantly modulated the effect of alcohol intake on BP (SBP and DBP).
Conclusions:
- Adipose tissue levels of ADH1A, ADH1B, and CYP4 enzymes involved in omega oxidation correlate with hexadecanedioate levels.
- Hexadecanedioate appears to mediate the impact of alcohol consumption on blood pressure.