Elevated blood fat levels may increase risk of sarcoidosis: Study
High triglyceride, LDL cholesterol levels point to higher risk
Elevated blood levels of fatty molecules, or lipids — specifically triglycerides and low-density lipoprotein cholesterol (LDL-c), also known as bad cholesterol — may be linked with an increased risk of developing sarcoidosis, while certain lipid-lowering medications may help reduce the risk.
That’s according to a study that looked at potential links between lipid levels and genetic variants strongly associated with sarcoidosis, and between genetic variants linked to effects simulating certain lipid-lowering medications and genetic variants associated with sarcoidosis.
The study, “Genetic association of lipids and lipid lowering drug target genes with sarcoidosis,” was published in Scientific Reports.
The researchers said they plan to conduct appropriately controlled trials on lipid-lowering medications in the future, as “identifying elevated lipid blood levels during the treatment of sarcoidosis patients may be useful.”
Sarcoidosis is marked by the formation and accumulation of small clumps of inflammatory cells, called granulomas, in the body’s tissues, most commonly the lungs. Previous studies indicated that sarcoidosis patients have significantly lower levels of high-density lipoprotein cholesterol (HDL-c), also known as good cholesterol, and that such lower levels may increase risk of the disease.
Blood fat and lung diseases
“A large number of studies have shown that changes in lipids and their metabolism can lead to chronic lung diseases and progression such as pulmonary fibrosis,” a disease marked by scarring in the lungs, the researchers wrote.
However, the role of these changes, as well as the role of lipid-lowering medications, in sarcoidosis patients “remains to be further studied,” the researchers wrote.
The team of scientists in China turned to a method called Mendelian randomization to evaluate whether blood lipid levels and lipid-lowering medications can affect the risk of developing sarcoidosis. Mendelian randomization uses genetic information to identify potential cause and effect relationships between an exposure — in this case, blood lipid levels or lipid-lowering medications — and an outcome, in this case the development of sarcoidosis.
They drew on publicly available, pooled genetic data from genome-wide association studies, which are designed to detect associations between genetic variants and a certain trait or disease. The studies covered 217,758 people of European descent.
They first looked for gene variants associated with sarcoidosis, and assessed whether different levels of fatty molecules in the blood, obtained from a freely available European database, influenced sarcoidosis risk based on the presence of those variants.
Results showed that increased blood levels of triglycerides were significantly associated with a 28.7% higher risk of sarcoidosis, and that higher LDL-c levels were significantly linked to a 23.2% increased risk.
No significant associations were observed between total cholesterol levels or HDL-c and the risk of sarcoidosis.
The findings indicate that LDL-c and triglycerides levels “may potentially serve as test parameters for predicting sarcoidosis risk and could be tested in future studies for their discriminative ability in this regard,” the researchers wrote.
The data also suggest that “lowering [blood triglycerides] levels and [blood] LDL-c levels may reduce the risk of sarcoidosis,” they added.
The team then looked at lipid-modulating variants in genes that are known targets of medications used to lower certain lipids — used as proxies for the effects of these treatments.
They found that higher LDL-c levels associated with variants in the PCSK9 gene, a target of a class of LDL-c-lowering medications called PCSK9 inhibitors, were significantly associated with a 68.1% higher risk of sarcoidosis.
Higher triglycerides levels linked to variants in the LPL gene, a target of triglycerides-lowering drugs, were also significantly associated with a 56.9% higher sarcoidosis risk.
These results suggest that “PCSK9-mediated reduction of LDL-C levels (simulating the effects of PCSK9 inhibitors) and LPL-mediated reduction of [triglycerides] levels (simulating the effects of LPL-related lipid lowering drugs) can decrease the risk of developing sarcoidosis,” the researchers wrote.
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