Evaluating association and transmission of eight inflammatory genes with Viliuisk encephalomyelitis susceptibility

Authors: Oleksyk, T. K.; Goldfarb, L. G.; Sivtseva, T.; Danilova, A. P.; Osakovsky, V. L.; Shrestha, S.; O'Brien, S. J.; Smith, M. W.

Source: European Journal of Immunogenetics, Volume 31, Number 3, June 2004 , pp. 121-128(8)

Publisher: Wiley-Blackwell

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Abstract:

Summary

Since the discovery of Viliuisk encephalomyelitis (VE) in 1887, scientists have tried to understand the natural history and aetiology of this endemic neurological disorder among the native Sakha population of Central Siberia. Familial aggregation and segregation analysis suggested a genetic influence on VE incidence. However, recent studies have implicated an unknown virus, possibly from the alpha herpesvirus family, as a possible cause for this disease. As VE is a neurological disease characterized by the inflammatory reactions systematically observed in the spinocerebellar fluid and in the brain tissue of deceased patients, we examined 17 single nucleotide polymorphisms (SNPs) across seven inflammation-related candidate gene regions, including chemokine receptors type 2 and 5 (CCR2/CCR5), interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-6, IL-10, stromal cell-derived factor (SDF) and chemokine regulated upon activation, normal T-cell expressed and presumably secreted (RANTES). Our main objective was to analyse the degree of genetic association between VE and candidate genes that have been previously implicated in other inflammatory diseases. Samples were collected from 83 affected families comprising 88 verified VE cases, 156 family members, and an additional 69 unrelated, unaffected inhabitants of the same geographical area. This collection included substantially all of the cases that are currently on the VE Registry. The experimental design included both case–control and transmission/disequilibrium test (TDT)-based familial association analyses. None of 17 SNPs analysed was significantly associated with VE occurrence. Exclusion of these eight genes based on the lack of association has important implications for identifying the disease agent, as well as prescribing therapy and understanding Viliuisk encephalomyelitis.

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1365-2370.2004.00459.x

Publication date: June 1, 2004

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