London - Genetic analysis of more than million people has tripled the number of known genetic locations that affect blood pressure. The genetic variants presented in Nature Genetics (2018; doi:) explain almost third of the hereditary influence.
High blood pressure is not only the result of an unhealthy lifestyle and other environmental influences. Heritability in twin and family studies was around 40%. Earlier genome-wide association studies (GWAS) had already identified 274 gene locations in which gene variants, so-called single nucleotide polymorphisms (SNP), influence blood pressure. A team led by Mark Caulfield from Queen Mary University and Paul Elliott from Imperial College London has now increased the number to 901. If you add few "secondary" signals, you come across just over 1,000 sites in the genome that have an effect on blood pressure.
The researchers compared the genes of more than million people in the largest GWAS to date, with the UK Biobank with 502,620 participants and the International Consortium of Blood Pressure Genome Wide Association Studies with 299,024 participants accounting for the majority .
The genetic variants were associated with 13 mmHg higher systolic blood pressure. The tenth of the people with the highest values in genetic risk score had 3.34-fold increased chance of high blood pressure and 1.52-fold increased risk of cardiovascular events.
Functional analyzes showed that large number of different factors have an effect on blood pressure. The TGF-beta signaling pathway is involved in several ways. It influences the excretion of sodium via the kidneys and the remodeling of the heart muscle. Another study recently discovered that serum TGF-beta levels correlated with blood pressure.
Other genes such as CTNNB1 influence the production of aldosterone in the adrenal cortex. The gene for vascular endothelial growth factor A (VEGF A) can change the structure and remodeling of blood vessels. Genes such as APOE and LRP4 encode components of lipoproteins that are used to transport lipids in the blood. Variants here could promote atherosclerosis.
Some gene variants indicate new treatment options. For example, people with variants in the SLC5A1 gene, which encodes sodium / glucose cotransporter in the kidneys, could benefit from treatment with canagliflozin. In fact, one of them found that the active ingredient approved for the treatment of type 2 diabetes lowers blood pressure.