Researchers Identify Gene Regions with High Levels of Proteins Linked to MS

A genome-wide study has identified DNA regions associated with higher levels of circulating cytokines, small proteins that pay a role in inflammatory diseases such as multiple sclerosis (MS).

Alterations in the levels and interplay of cytokines and growth factors play a key role in several inflammatory diseases, including MS. Cytokines help regulate cell signaling. Growth factors are substances such as vitamins or hormones that stimulate cell growth.

Scientists want to obtain a better understanding of the interplay between cytokines and growth factors to gain insight into inflammatory diseases.

The study, “Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors,” was published in The American Journal of Human Genetics.

Researchers performed a genome-wide association study (GWAS) involving 8,293 Finns. GWASes help scientists identify small regions within our DNA that vary between people, and may associate with a certain disease.

Scientists from the Research Center of Applied and Preventive Cardiovascular Medicine at the University of Turku in Finland investigated links between levels of 41 circulating cytokines and growth factors and 10.7 million DNA variations.

“We wanted to find out the molecular-level processes that lead to an increased risk of developing inflammatory diseases. Understanding these processes will enable more effective treatment of diseases,” Professor Olli Raitakari, director of the research center and one of the study’s senior authors, said in a press release.

Researchers identified 27 genomic regions that have a significant association with circulating cytokines. They also identified a genomic variation associated with higher production of the circulating interleukin-2 receptor alpha subunit (IL-2ra). This variation increases the risk that someone will develop Crohn’s disease and MS.

Daclizumab, an FDA-approved MS treatment sold in the United States as Zinbryta, is a humanized monoclonal antibody targeting IL-2ra. It has been shown to cut the relapse rate in MS in half, compared with controls receiving placebos.

“Our results suggest that Zinbryta might be beneficial for persons with Crohn’s disease as well,” the researchers wrote.

The research identified DNA regions that may regulate the concentration of inflammation-promoting cytokines in our blood.

“We identified a total of 27 loci [genomic regions] contributing to the genetic regulation of circulating concentrations of cytokines. Improved understanding of the genetic basis of these inflammatory markers will help to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases,” the researchers wrote.