New Inflammatory Marker Genome Links Identified

New links between the human genome and inflammation tracers have been found by researchers in Finland. In a study of over ten million DNA variations, new possibilities for treatment of diseases such as multiple sclerosis, Crohn’s disease and celiac disease were uncovered.

Researchers at the Research Centre of Applied and Preventive Cardiovascular Medicine at the University of Turku, Finland noticed that the medicine daclizumab, previously used for treating organ rejection reactions, could possibly also be used in the treatment of multiple sclerosis and Crohn’s disease.

In addition, an increase in the activity of MIP1b-cytokine could also serve as a method of treatment against celiac disease and Behcet’s disease. Further clinical studies are required to confirm the observations.

Cytokines And Inflammatory Disease

Cytokines and growth factors, which circulate in the bloodstream, are important proteins for regulating inflammation reactions. Changes in their mode of operation have been linked with many inflammatory diseases, such as Crohn’s disease, multiple sclerosis, atherosclerosis, ulcerative colitis and many types of cancer.

In this latest study, based on population data and coordinated by the University of Turku’s Research Centre of Applied and Preventive Cardiovascular Medicine, an investigation was made of the links between 41 different 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”,

explains Professor Olli Raitakari, Director of the Research Centre.

Evidence From Human Genetics

Technological development has enabled the practice of genome-wide association studies since the turn of the century.

In these kinds of studies, millions of DNA variations are examined and their impact is assessed for each property being studied. The studies carried out so far have succeeded in uncovering, for example, over one hundred positions of genes on chromosomes which have an impact on the risk of developing Crohn’s disease or ulcerous colitis.

In studies of connections between genetic variations and disease risks, the precise molecular process causing the increased risk often remains unclear. In order to uncover this molecular process, 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.

“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. 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,”

Professor Raitakari points out.

Ari V. Ahola-Olli, Peter Würtz, Aki S. Havulinna, Kristiina Aalto, Niina Pitkänen, Terho Lehtimäki, Mika Kähönen, Leo-Pekka Lyytikäinen, Emma Raitoharju, Ilkka Seppälä, Antti-Pekka Sarin, Samuli Ripatti, Aarne Palotie, Markus Perola, Jorma S. Viikari, Sirpa Jalkanen, Mikael Maksimow, Veikko Salomaa, Marko Salmi, Johannes Kettunen, Olli T. Raitakari
Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors
The American Journal of Human Genetics, 2017; 100 (1): 40 DOI: 10.1016/j.ajhg.2016.11.007

Image: Peter Lane and Fiona McConnell, Wellcome Images

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