Genes serve as the intricate orchestrators of our health. By better understanding our genetic makeup, we gain invaluable insights into how our genes shape and affect us. Yet the genetic realm is still complicated; we’re constantly working to learn more about the undiscovered impact of our genes. A recent revelation from the University of Southern California’s Leonard Davis School of Gerontology brings to light how our genetics can actually confer protection against certain diseases. As the University reports, a recently published study has uncovered a previously unidentified and naturally occurring genetic variant that reduces the risk of Parkinson’s disease development by around 50%. This breakthrough emphasizes the complexity of our genetic makeup while underscoring the potential to develop and guide future treatments and protective therapies.

Protecting Against Parkinson’s: The Next Frontier

The study, which was published in Molecular Psychiatry, sought to evaluate the relationship between Parkinson’s disease and mitochondrial DNA single nucleotide polymorphisms (mtSNPs). Prior studies suggested that mtSNPs reduce the risk of Parkinson’s development. Parkinson’s disease is a progressive neurodegenerative disorder that affects dopaminergic (dopamine-producing) neurons in the brain. Mostly occurring in people above 50 years old (though it can occur in younger individuals), Parkinson’s disease is characterized by tremors, slowed movement, muscle rigidity, impaired balance and posture, speech alterations, mood changes, constipation, and hallucinations and delusions in later years.

Prior studies found that mtSNP m.2158 T > C is protective against Parkinson’s disease and that SHLP2 in general is protective against aging-related diseases. As the more recent study explains, researchers wanted to identify:

the effects of the m.2158 T > C allelic form of SHLP2 (termed K4R SHLP2) on mitochondrial function. Elucidating mechanisms by which SHLP2 and the K4R variant impact mitochondrial function may guide novel therapeutic modalities focused on restoring mitochondrial function in PD.

The research team screened data from 9,744 individuals within the Cardiovascular Health Study, Framingham Heart Study, and Health & Retirement Study with a particular focus on K4R SHLP2. After identifying individuals who had this gene variant, the research team discovered that:

• The K4R mutation acts as a “gain-of-function” variant. This means that the body more highly expresses SHLP2 and that the SHLP2 microprotein was more stable and more protective against mitochondrial dysfunction. SHLP2 also binds more favorably and stably to mitochondrial complex 1, an important enzyme.
• People with this mutation were around 50% less likely to develop Parkinson’s disease than people without this mutation.
• The K4R variant is more common in people of European ancestry.