Genomic Population Analysis Identifies Loci Influencing Inflammatory Diseases

February 2, 2017
Genomic Population Analysis Identifies Loci Influencing Inflammatory Diseases
Source: NIH

Investigators from the Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC) at the University of Turku, Finland, have studied over ten million DNA variations and recently found new links between the human genome and inflammation tracers. The new study—published recently in the American Journal of Human Genetics through an article entitled “Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors”—uncovers new possibilities for treatment of disorders such as multiple sclerosis, Crohn's, and celiac disease.

“We wanted to find out the molecular-level processes that lead to an increased risk of developing inflammatory diseases,” explained senior study investigator Olli Raitakari, Ph.D., director of CAPC. “Understanding these processes will enable more effective treatment of diseases.”

Circulating cytokines and growth factors are important proteins for regulating inflammatory reactions. Changes in their mode of operation have been linked to a variety of inflammatory diseases and even various types of cancer. In this latest study, based on population data, researchers established links between 41 different cytokines and growth factors and 10.7 million DNA variations.

“In these kinds of studies, millions of DNA variations are examined, and their impact is assessed for each property being studied,” Dr. Raitakari noted. “The studies carried out so far have succeeded in uncovering, for example, over one hundred genomic loci which have an impact on the risk of developing Crohn's disease or ulcerative colitis.”

Interestingly, the investigators noticed that the medicine daclizumab, previously used for treating organ rejection reactions, could be used in the treatment of multiple sclerosis and Crohn's disease. Moreover, an increase in the activity of MIP1b-cytokine could also serve as a method of treatment of celiac disease and Behcet disease.

In studies of connections between genetic variations and disease risks, the precise molecular process causing the increased danger often remains unclear. In order to uncover this mechanism, genome-wide association studies use as response variables molecules that mediate disease-risk through the bloodstream, such as cytokines and growth factors, instead of using the diseases themselves. The data used in the study was composed of internationally unique long-term research data covering risk factors for cardiovascular diseases among Finns.

“It has been shown that for those drug candidates, where there is evidence from human genetics of their effectiveness, the chance of being approved in clinical studies testing effectiveness and safety is increased two-fold,” Dr. Raitakari pointed out. “Various estimates made of the costs of developing for market a single medicinal molecule have come out at around 800 million dollars. Genetics research can offer significant savings for medical development.”