Genetics Behind Cardiovascular Fitness May Increase ALS Risk, Study Reports

Magdalena Kegel avatar

by Magdalena Kegel |

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ALS genes and fitness

Amyotrophic lateral sclerosis (ALS) may be linked to genetic factors that promote cardiovascular fitness, according to a study indicating that ALS patients’ parents died of cardiovascular disease less often.

But researchers underscored that it is not physical activity that increases the risk of ALS.

The study, “Exploring the fitness hypothesis in ALS: a population-based case-control study of parental cause of death and lifespan,” was published in the Journal of Neurology, Neurosurgery, and Psychiatry.

Many studies have noted that most ALS patients do not have health issues linked to abnormal metabolism, such as obesity, high blood pressure, heart disease, diabetes, and stroke.

A research team at the University Medical Center Utrecht had also found a connection between more leisure time ALS, but no connection between occupation-related physical activity and the disease. This somewhat odd finding suggested that lifestyle factors linked to physical activity had no impact on the risk of developing ALS. Rather, the team hypothesized that genetic factors that made it more likely to be both physically active and develop ALS were at play.

To test the idea, the research team recruited 487 patients with ALS and 1,092 controls for a study that focused not on the patients but on their parents. Using questionnaires, the team gathered information about the causes and times of the parents’ deaths.

Cardiovascular disease was more often the cause of the controls’ deaths than the deaths of the ALS patients’ parents. The parents’ smaller rate of cardiovascular death was not linked to their lifetime physical activity, researchers said.

The team figured there were at least three ways to explain their observations. The first possibility was that a genetic profile that facilitated physical fitness might increase physical activity, which in turn might increase the risk of ALS. The team deemed that scenario unlikely because it found no links between physical activity and cardiovascular death.

Another possibility — and the one they believe most likely — is that certain genes may both increase the risk of ALS and promote cardiovascular fitness.

Their third possible explanation is that genetics, perhaps together with physical activity, could activate metabolic pathways. That activation could promote cardiovascular health while increasing the risk of ALS.

Because these explanations are just theories, the team said the relationships need to be explored in future studies. “In summary, exploring the fitness hypothesis in the pathogenesis of ALS, our findings provide evidence for a shared mechanism underlying a favourable cardiovascular fitness profile and ALS susceptibility,” the authors concluded.