Dr. Toyoda and his colleagues in Japan have described new susceptibility genes–CCR1 and CCR3–for type 1 narcolepsy.
Type 1 narcolepsy (also called narcolepsy with cataplexy) is believed to be the result of a combination of genetic and environmental factors that leads to autoimmune destruction of cells in the brain that make hypocretin. Most, but not all, people with type 1 narcolepsy carry the HLA-DQB1*06:02 allele. However, many people without narcolepsy also have the HLA-DQB1*06:02 allele, which suggests that other factors, likely related to immune function, are involved in the development of narcolepsy.
Who were the participants and what did they do?
All of the people in this study were Japanese living in Japan. Those with narcolepsy had excessive daytime sleepiness and clear-cut cataplexy. They had not been diagnosed with any sleep, neurological, or psychiatric disorder other than narcolepsy. All of them were positive for the HLA-DQB1*06:02 allele. All comparison participants (who did not have narcolepsy) were unrelated healthy people.
Who were the researchers and what did they do?
Dr. Toyoda and his colleagues at the University of Tokyo obtained blood samples from all participants. They first used a genome-wide association study (GWAS) to examine blood samples from 409 people with narcolepsy and 1562 healthy people without narcolepsy (comparison participants) to identify potential single nucleotide polymorphisms (SNPs) that might be associated with narcolepsy. They next confirmed the findings from the GWAS in a different sample of 240 people with narcolepsy and 869 control subjects. One of the SNPs, rs3181077, was located close to the chemokine receptor 1 and 3 (CCR1/CCR3) transcription sites, which suggests it would be related to the expression of these genes. The researchers then measured the messenger RNA of CCR1/CCR3, finding reductions in patients with narcolepsy. To further confirm that this polymorphism affected immune function, the researchers demonstrated that it was also associated with reduced movement of stimulated immune cells.
What are the authors’ conclusions?
Our findings provide evidence for the involvement of impaired CCR1/CCR3 functions in the etiology of narcolepsy.
Toyoda, H., et al. A polymorphism in CCR1/CCR3 is associated with narcolepsy. Brain Behav Immun. (2015), http://dx.doi.org/10.1016/j.bbi.2015.05.003.