Dale Lloyd II, No. 39. (The Rice Football Webletter)

On a mild September afternoon in 2006, 19-year-old cornerback Dale Lloyd II stepped onto the practice field for a conditioning workout with the Rice University football team. After running 16 consecutive sprints of 100 yards each, he collapsed. He died the next day from acute exertional rhabdomyolysis (ER) associated with a genetic condition called sickle cell trait. Lloyd did not know that he had the sickle cell trait, yet if he had known, some simple precautions could have saved his life. In order to keep other young athletes from suffering the same fate, Lloyd’s parents filed a wrongful death lawsuit in September 2008 against Rice University and the National Collegiate Athletic Association (NCAA).

Lloyd did not know that he had the sickle cell trait, yet if he had known, some simple precautions could have saved his life.

When the lawsuit was settled in June 2009, the NCAA agreed to require that, beginning in the 2010-2011 academic year, all Division I athletes undergo testing for sickle cell trait (PMID 20825310). It is estimated that this will ultimately affect more than 160,000 athletes.

This rare risk of sudden death for those with sickle cell trait is a vivid example of how a person’s genes and lifestyle or environment play important roles in determining the risk of disease.

The Differences Between the Disease and the Trait

While normal people have two copies of the normal hemoglobin gene (HbA/HbA), those with sickle cell disease have two copies of the sickle cell gene (HbS/HbS). Those with sickle cell trait, called carriers, have one copy of the normal gene and one copy of the sickle cell gene (HbA/HbS).

In sickle cell disease, the red blood cells become crescent-shaped, or sickled, and clump together, sticking to blood vessel walls and blocking blood flow within limbs and organs. Associated with a decreased lifespan, sickle cell disease is a lifelong chronic condition that can cause painful episodes and lead to permanent organ damage (PMID 20301551, PMID 21131035). On the other hand, those with sickle cell trait have a normal lifespan, are asymptomatic and in the absence of extreme physical exertion, can lead normal, healthy lives.

Sickle Cell Trait and Exertional Rhabdomyolysis

Exertional rhabdomyolysis (ER) is a condition in which muscle cells break down and release myoglobin and cell enzymes into the blood, causing kidney damage and eventual death from kidney failure (PMID 16558353). Symptoms of ER include muscle weakness or swelling, muscle pain and/or cramping and tea-colored urine.

Although ER does occur in normal, healthy individuals following strenuous exercise, the risk of sudden death from the condition is much greater in individuals with sickle cell trait, especially under conditions of extreme heat and humidity, high altitude, exercise-induced asthma and pre-event fatigue (PMID 16558353). In a study of exercise-related death unexplained by preexisting disease among African American military recruits, Kark and Ward (1994) found that individuals with sickle cell trait were 30 times more likely to die than individuals with normal hemoglobin genes (PMID 7973777).

Precautions

Despite the rare, but potentially fatal health risk posed by extreme physical exertion in those with sickle cell trait, there is no reason to exclude these people from participating in sports. This is made very clear in recommendations from the NCAA. In fact, individuals with sickle cell trait can compete and play sports at all levels, as all incidents of sudden death among athletes with sickle cell trait have involved conditioning sessions rather than skill practice sessions or actual games.

According to NCAA recommendations, those with sickle cell trait need to take some simple precautions, such as following a slow and gradual preseason conditioning schedule and slowly building the training intensity. Other NCAA recommendations include using adequate rest and recovery sessions between repetitions — especially during all-out exertion drills — as well as stopping activity and notifying trainers and coaches if athletes experience muscle pain, abnormal weakness, undue fatigue or breathlessness. Click here for additional NCAA recommendations and information.

Sickle Cell Trait: Carriers and Testing

African Americans are the largest ethnic group to carry the sickle cell trait. According to the California Department of Public Health and its data derived from screening nearly 7.5 million newborns in California , 1 in 15 African Americans have the sickle cell trait. For other ethnic groups, the proportion of people with sickle cell trait are 1 in 150 Native Americans, 1 in 203 Hispanic Americans, 1 in 478 individuals of Middle Eastern descent, 1 in 642 Caucasians, 1 in 652 Asian Indians, 1 in 879 Filipinos, 1 in 1,315 Asians and 1 in 2,365 Southeast Asians.

A simple biochemical test called the sickle cell solubility test is used for the sickle cell trait screening mandated by the NCAA. DNA testing, such as the testing conducted in Pathway’s Pre-Pregnancy Planning Insight genetic testing service, can also determine if a person carries the sickle cell trait.

This is not the first time sickle cell trait testing has been conducted on a population-wide basis. Screening for sickle cell trait among African Americans was first carried out in the 1970s, but the testing was poorly designed and failed to clearly explain the distinction between sickle cell trait and sickle cell disease. The result was the stigmatization of African Americans and of people carrying sickle cell trait (PMID 1497018). Today, all states test newborns for sickle cell disease (PMID 20207263).

The Ball is in Your Hands

One thread that runs though Pathway’s personal genetic reports is that diseases result from an interaction between a person’s genes and his or her environment or lifestyle. With this post, we hope to have raised your awareness about this interaction with the example of how sickle cell trait can have serious, and even fatal consequences, under certain rare, but nevertheless real life circumstances. Although we have no say on the genes we were born with, we do have control over our own lifestyles, the choices we make, and our environment. That is why Pathway strives to provide physicians and their patients with actionable lifestyle recommendations in the genetic testing reports we provide.

While eating disinhibition describes a person’s tendency to eat more than normal in response to a stimulus, food desire, on the other hand, is measured by the amount of effort a person is willing to expend to get their favorite foods.  Said another way, eating disinhibition describes someone who chows down on snacks at a party, while food desire describes someone who drives 20 minutes out of their way to get their favorite barbecue.

Eating disinhibition occurs when a person loses control and overeats, which can occur when a person’s favorite foods are available, in times of emotional stress, or in social gatherings. In a 2010 study involving 729 people (381 females and 348 males), researchers examined the association between eating disinhibition and the rs1726866 marker in the TAS2R38 gene. This association was found only within the female participants in the study (PMID 19782709).

For food desire, on the other hand, there are no objective methods to quantify an individual’s fondness for certain foods. Despite this hurdle, behavioral scientists are able to measure an individual’s motivation to consume food and compare it to others’ motivations to consume food. This method of measurement is called the reinforcing value of food, and it evaluates the effort an individual is willing to expend to access his or her favorite foods (PMID 16257474).

The reinforcing value of food can be measured through a series of tests. In each of these tests, the person being examined is requested to complete a task in exchange for a small portion of his or her favorite foods. Initially, the task of obtaining the food is not difficult because the tasks are simple. But, as the tests continue, the tasks become more and more difficult, and eventually the person will stop trying to complete the tasks because the food is no longer worth the effort – the reward no longer holds its power to that person. The point of this experiment is that individuals who quit later in the series, compared with individuals who quit earlier, are high in food reinforcement.

In a 2007 study, researchers analyzed the reinforcing value of food in the eating behaviors of 74 participants who completed a questionnaire, participated in food reinforcement task sessions, and underwent genetic testing. Among 29 obese subjects in the study, those who had the T allele at the rs1800497 marker (which affects dopamine activity) were more likely to exhibit increased levels of food reinforcement. The study also concluded that individuals with high food reinforcement were more likely to have higher energy intake (i.e., food intake) compared to individuals with lower food reinforcement (PMID 17907820). So, if you have high food reinforcement, you are more likely to eat more.

What do you do if you find out your genetics predispose you to eating disinhibition or food desire? If your genetics show that you may be eating disinhibited, try to figure out what stimulates overeating for you. For example, if you eat more during social situations, or when you’re stressed out, you’ll know these are times when you need to really strengthen your willpower. If you have food desire, try keeping healthy foods close by, and move the unhealthy tempting foods out of easy reach.

Learn more about eating behaviors and Pathway Fit™…