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Although the pathogenesis of progressive degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease remains uncertain, cytokines are thought to contribute to the development of the disease.1 Interferon (IFN)-γ is one of the Th1 cell derived multifunctional cytokines and seems to influence neuronal differentiation and to increase in inflammatory and neurodegenerative diseases.2 Immunohistochemical studies showed an increase of IFN-γ expression in nigral astrocytes of patients with Parkinson's disease.3 This increase of IFN-γ concentration may be a trigger for the disease or a compensatory response. It was reported that IFN-γ producing capacity in whole blood cultures of untreated parkinsonian patients decreased compared with sex and age matched healthy controls.4 This supports the idea that IFN-γ may increase in Parkinson's disease as a compensatory response. Concerning genetic polymorphisms in the IFN-γ gene, the production of IFN-γ measured in peripheral blood mononuclear cell cultures may correlate with dinucleotide CA repeat polymorphism in the first intron of the IFN-γ gene.5 In vitro production of IFN-γ is higher in people homozygous for allele 122 (12 CA repeats, named allele 2 by Pravica et al 5 and allele 6 by Awata et al 6) than in those of other genotypes.5 Therefore, we investigated the CA repeat polymorphism of the IFN-γ gene in 170 patients with idiopathic Parkinson's disease (102 women and 68 men, aged 64.2 (SD 9.7) years; onset, 55.5 (SD 10.6) years; disease duration 8.7 (SD 5.2) years). As controls, 157 healthy people were selected from the annual health examination at a city clinic. The control group was matched for age (mean: 62.5 (SD 8.7) years), sex ratio (98 women and 59 men), and birth place (Kyoto and Osaka prefectures) with the patients. All participants were Japanese. The study protocol was approved by the institutional ethics committees and informed consent was obtained from every participant. The CA repeat polymorphism was analyzed according to a previous report.6 The result is shown in table 1. Using χ2 analysis (combined rare alleles “116”, “118”, “130”, and “132”), no significant difference was found in allele distribution between the Parkinson's disease and control groups (p=0.86). When patients were divided into two groups (early onset and late onset disease), pc was obtained by multiplying the p value by two. No significant difference was found between patients with early onset Parkinson's disease and controls (pc=0.23) or between those with late onset Parkinson's disease and controls (pc=1.17). However, the allele distribution was significantly different between early onset (<50 years) and late onset (⩾50 years) disease (χ2=14.3, df=5, pc=0.028). The frequency of allele 122 was lower in those with early onset Parkinson's disease than in those with late onset Parkinson's disease. Carriership analysis also showed a low allele 122 carrier frequency in patients with early onset compared with late onset disease (χ2=4.62, df=1, pc=0.039). Although the genetic polymorphism of IFN-γ does not seem to be a risk factor for Parkinson's disease, a lack of high producer allele 122 may affect the onset of disease. The allele 122 may be part of a haplotype that also includes functionally relevant polymorphisms. Our findings support the idea that the increase of IFN-γ concentration in the brain of patients with Parkinson's disease might be a compensatory response rather than a trigger of the disease. Thus, IFN-γ might be helpful in delaying the progress of the disease.
This work was supported in part by grants in aid from the Ministry of Health and Welfare of Japan (Health Science Research Grants, Research on Brain Science and a grant in aid for Neurodegenerative Disorders).