Salt sensitivity of blood pressure (BP) is an independent cardiovascular disease (CVD) and mortality risk factor, present in both hypertensive and normotensive population. Better understanding of this phenotype in healthy individuals may lead to more effective prevention of hypertension and CVD. Salt sensitivity is genetically determined and it may affect the relationship between salt taste perception and salt intake. This thesis, for the first time, comprehensively explored the associations between genetics, salt sensitivity of BP, salt taste perception and salt intake as well as the potential of using genetic information in salt sensitivity biomarker development. The study population comprised young to middle-aged, healthy adults. Salt sensitivity was defined as the change in BP after seven days of low-salt (51 mmol sodium/day) and seven days of high-salt diet (308 mmol sodium/day). Salt taste perception was identified using British Standards Institution sensory analysis method (BS ISO 3972:2011). Salt intake was assessed with a validated food frequency questionnaire and two 24-hour dietary recalls based on the 5-step multiple pass method. DNA was genotyped for single nucleotide polymorphisms (SNPs) in the SLC4A5, SCNN1B and TRPV1 genes coding for sodium and ion channels and transporters. Protein levels were measured from urinary exosomes with the focus, for the first time, on methods readily used in clinical setting, such as enzyme-linked immunosorbent assay (ELISA). Results showed that the participants with AA genotype of the rs7571842 (SLC4A5) exhibited the highest increase in BP (ΔSBP = 7.75 mmHg, p = 0.002). There was no association between genetics and salt taste perception as well as genetics and salt intake. No associations were observed between salt sensitivity of BP, salt taste perception and salt intake. These results warrant further investigation in a larger sample size study. Nevertheless, preference for salty taste or awareness of health risks related to increased salt intake may be a driver of salt intake in younger and healthy population and warrants further investigation. The involvement of SLC4A5 in salt sensitivity of BP, together with functional effects of the investigated SNPs, makes it a candidate for genetic and physiological marker of salt sensitivity. The ELISA measurement of its expression from urinary exosomes may serve as a method of choice in a clinical setting, if further optimised.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:766916 |
| Date | January 2018 |
| Creators | Pilic, Leta |
| Publisher | St Mary's University, Twickenham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://research.stmarys.ac.uk/2934/ |
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