©2016 by UVa Health System. Division of Endocrinology.

GENETICS

AND

YOUR HEALTH

 What effect do your genes have on you?

Genes are hereditary units that are passed down from parent to child and are the basis of our genetic composition. An understanding of your genes can provide a preventative measure against future risk of detrimental health. Genes are your body's blueprint. They provide instructions on what should be made, the function, and how those cells react to changes in the body. This interaction is the basis of homeostasis - the concept of keeping chemical or nutritional levels of the body at a healthy balance in order to maintain equilibrium.
 

Why this study applies to you

High blood pressure, or hypertension, is defined as a systolic blood pressure over 139 mm Hg and diastolic blood pressure over 89 mm Hg.  One-third of the world’s population has high blood pressure (hypertension) and it is responsible for almost 62% of deaths from stroke and 49% of deaths from coronary heart disease. Salt sensitivity is defined as in increase of blood pressure after a high salt meal.  Salt sensitivity of blood pressure is equally devastating since it affects over 25% of the adult population and can reduce life expectancy by 20 years. However, the diagnosis of salt sensitivity cannot be performed in a doctor’s office setting due to its complexity and cost.  Even individuals with normal or low blood pressure can be salt sensitive.  The relationship between salt intake and cardiovascular risk is not linear, but rather fits a J-shaped curve relationship. Thus, a low-salt diet may not be beneficial to everyone and may paradoxically increase blood pressure in some individuals.

 

Accurate testing of salt sensitivity is not only laborious but also expensive, and with low patient compliance. Patients who have normal blood pressure but are salt-sensitive cannot be diagnosed in an office setting and there are no commercially available laboratory tests for salt sensitivity. Urinary surrogate markers for salt sensitivity are being developed and tested in our clinical study.

 

Our clinical study is designed to test the effect of two kidney gene variants on the degree of salt sensitivity of individuals. A polymorphism is one of many different forms of mutations in a single gene. We are looking for three polymorphisms in a protein called GRK4 that has been associated with hypertension and salt sensitivity. In addition, we are examining the effect of polymorphisms in a protein called NBCe2 that assists with sodium metabolism in the kidney. Polymorphisms in the gene for NBCe2 are associated with the increased likelihood of salt sensitivity. Clinical study participants that do not have any of these polymorphisms (controls) will be compared to individuals who express various combinations of these polymorphisms.   As a volunteer for this study, we will test you for the presence of these polymorphisms at no charge and invite you to participate in  a two week study with controlled dietary salt intake under our supervision, if you have the right genetic profile.

Our clinical study tests the effect of two kidney gene variants with the degree of salt sensitivity of an individual. Specifically, we are looking at the different forms of the genes GRK4 and the gene that encodes the information for the NBCe2 protein. Keep reading to learn more about what genes are and how they work.

Be proactive and learn about your susceptibility to developing hypertension in the future

Basic Overview:

What is a Gene?

Basic Overview:

Differences in Genes and their Proteins

As a contextual example, let's look at the kidney. Because the goal is maintaining equilibrium, the kidney is responsible for excreting wastes and excess nutrients within the body such as sodium. Genes provide information on how proteins, cells, and therefore tissues such as the kidney function. Genes vary from person to person and mutations can arise that alter proper function. If a mutation in the genetic material of the kidney were to arise where sodium excretion was not properly regulated, there could be an unhealthy increase in sodium levels within the body. An increase in sodium levels may result in the decrease in water excreted from the body. A build up of bodily fluid causes blood pressure to increase because your heart is working harder to pump the excess across the body. This minor modification in function can result in a snowball effect of negative outcomes such as blood clots, stroke, heart failure, etc.

 Why does salt affect me differently than my friend

While we share 99.9% of our genetic information as humans, not everyone will have the same version of genes. The different forms of genes are called alleles, and the alleles for a gene can vary from person to person. Individuals have two alleles of one gene - one inherited from the mother, and the other from the father. Usually one allele is expressed preferentially over the other, which in genetics we call the dominant allele. When there are multiple differences in outward appearances from the same gene, this gene is considered to be polymorphic. For example, everyone has different facial features or hair color.

Although we can't see inside our bodies, differences in our genes mean not everyone can regulate sodium levels within their body the same way. Some kidneys are more effective in excreting sodium better than others. It is this difference that our team is interested in studying with more extensive research. The management of hypertension follows a linear path where treatment may not be beneficial to all. Understanding different polymorphisms can help the drug developmental process in alleviating the hypertensive crisis.