Metabolic Syndrome, Cause of Heart Disease and Diabetes, Linked To LRRK2 Mutations

Certain features of metabolic syndrome may be more prevalent in people with Parkinson’s disease-associated mutations in the gene LRRK2, new research suggests.

The research abstract “Metabolic syndrome and genetic Parkinson’s disease, the case of LRRK2 and GBA” was published online. It was to be presented at the 2020 annual meeting of the American Academy of Neurology, which was canceled due to the COVID-19 pandemic.

Metabolic syndrome is a group of co-occurring conditions associated with a higher risk of heart disease, diabetes, and other health problems. It is defined by the presence of three of the following five conditions: obesity, high blood pressure, prediabetes (where blood sugar is abnormally high, but not so high as to constitute type 2 diabetes), high blood levels of triglycerides (a type of fat), and low blood levels of HDL (the “good” cholesterol).

Previous research has suggested that metabolic syndrome or its individual components increase the risk of Parkinson’s disease, but the relationship between the two remains unclear.

These new findings come from an analysis of 562 people. Of them, 214 with diagnosed Parkinson’s, including 40 people with mutations in the LRRK2 gene and 70 with mutations in the GBA gene. Both genes are associated with this disease.

The remaining 104 Parkinson’s patients had idiopathic disease, meaning they didn’t have mutations thought to be associated with their disease.

The other 348 people included in the study did not have Parkinson’s; however, 55 had LRRK2 mutations, and 97 had GBA mutations. People in these two groups were termed non-manifesting carriers (NMCs): they had the respective mutation, but no disease was “manifest” as of this study.

No differences in the presence of metabolic syndrome or its components were seen among people with or without Parkinson’s in this analysis.

However, compared to those with idiopathic Parkinson’s or disease due to GBA mutations, Parkinson’s patients with LRRK2 gene mutations had significantly higher triglyceride levels and higher rates of prediabetes.

Non-manifesting carriers with LRRK2 mutations also had significantly higher triglyceride levels than did non-manifesting carriers with GBA mutations or those without mutations.

Sometimes, an individual can have some symptoms indicative of Parkinson’s, but without fully fulfilling diagnostic criteria for the disease. This is termed prodromal Parkinson’s disease.

Among non-manifesting carriers, those with high probability rates (over 50%) for prodromal disease had significantly higher frequencies of hypertriglyceridemia (elevated blood triglyceride levels) and prediabetes compared to those with lower probabilities of prodromal disease.

“While there is no difference between genetic PD [Parkinson’s disease] and NMC in the amount of [metabolic syndrome] components, elevated triglycerides and prediabetes were more frequent among LRRK2 carriers,” the researchers wrote.

They speculated that these components “might represent modifiable risk factors” for this disease, but further research is needed.