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Gene Expression Meta-analysis Leads to Blood Pressure Signature

NEW YORK (GenomeWeb) – An international team reporting in PLOS Genetics this week has tracked down blood gene expression signatures that coincide with blood pressure variation and hypertension.

From array-based profiles of blood gene expression for thousands of American or European individuals with known blood pressure measurements, the researchers narrowed in on transcripts with expression profiles that varied in concert with blood pressure — a collection that pointed to new and known blood pressure players.

The identified genes "may represent an early step toward improvements in the detection of susceptibility and in the prevention and treatment of hypertension, the study's authors argued.

The team reasoned that a large-scale look at gene expression might complement clues to blood pressure biology that have been gleaned from GWAS, which have already uncovered numerous loci linked to blood pressure traits.

The researchers explored this possibility using data for 7,017 individuals enrolled through half a dozen studies in the US and Europe. These participants previously had their systolic blood pressure, diastolic blood pressure, and body mass index measured and none were taking anti-hypertensive medication.

Between 11 and 45 percent of the individuals enrolled in each of the six trials were classified as having hypertension.

The team's analysis was based on expression profiles from whole-blood samples that had been generated using Illumina arrays for five of the cohorts. Individuals in the remaining cohort had their blood transcript levels tested with an Affymetrix array.

Together, these transcript patterns pointed to 34 genes showing differential expression patterns coinciding with blood pressure profiles. Of those, 27 transcripts typically showed elevated expression with rising blood pressure, while seven transcripts had lower-than-usual expression in the blood of individuals with higher blood pressure.

The collection included two genes implicated in blood pressure in the past. The other transcripts highlighted potential blood pressure-related contributions by several main pathways, including those regulating apoptosis, inflammatory response, and antigen profiles.

Next, the researchers compared expression quantitative trait loci (eQTL) for differentially expressed genes with the set of variants associated with blood pressure in the National Human Genome Research Institute's GWAS catalog and in International Consortium of Blood Pressure studies.

Although none of the blood pressure-associated SNPs fell at cis-eQTL near the differentially expressed transcripts, the team tracked down at least one example of a GWAS variant that appeared to have trans-eQTL activity.

That variant, which is in the SH2B3 gene, appeared to act as a distant regulator of six of the genes that displayed blood pressure-related expression shifts in the blood in the meta-analysis: FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2.

The study's authors argued that these six blood pressure signature genes, driven by the same blood pressure-associated eQTL, point to a "critical and previously unrecognized mechanism" involved in blood pressure regulation.

Along with further studies aimed at digging into that possibility, they called for additional research into the interplay between inflammation and blood pressure patterns, as well as work aimed at untangling transcriptional profiles found in other tissue types.