A polymorphism in CCR1/CCR3 is associated with narcolepsy.
Hiromi Toyoda1, Taku Miyagawa1, Asako Koike2
1Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Brain, Behavior, and Immunity
|May 20, 2015
Summary
Narcolepsy-cataplexy involves genetic and environmental factors. New research identifies chemokine receptor genes CCR1 and CCR3 as novel susceptibility genes, suggesting impaired immune function in patients.
Area of Science:
- Genetics
- Immunology
- Neurology
Background:
- Narcolepsy-cataplexy etiology is multifactorial, involving genetic and environmental influences.
- The human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is a known risk factor but not solely causative.
- Identifying additional non-HLA susceptibility genes is crucial for understanding narcolepsy.
Purpose of the Study:
- To identify novel, non-HLA genetic susceptibility factors for narcolepsy-cataplexy.
- To investigate the role of chemokine receptor genes in narcolepsy pathogenesis.
- To explore the association between genetic variants and immune function in narcolepsy patients.
Main Methods:
- Genome-wide association study (GWAS) in Japanese populations.
- Replication study using an independent sample set.
- Measurement of candidate gene mRNA levels in peripheral blood.
- In vitro chemotaxis assays to assess monocyte migration.
Main Results:
- A single nucleotide polymorphism (SNP) in the CCR1 promoter (rs3181077) was significantly associated with narcolepsy.
- CCR1 and CCR3 mRNA levels were reduced in narcolepsy patients compared to controls.
- Monocyte migration was impaired in individuals carrying the rs3181077 risk allele.
- CCR1 and CCR3 are identified as novel narcolepsy susceptibility genes.
Conclusions:
- Chemokine (C-C motif) receptor 1 (CCR1) and CCR3 are newly discovered susceptibility genes for narcolepsy.
- These findings suggest a role for CCR genes in narcolepsy pathogenesis.
- The results support the hypothesis of impaired immune function in narcolepsy-cataplexy.
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