711. Genetic Susceptibility to Neurological Complications of West Nile Virus Infection
Session: Abstracts: Virology
Friday, October 22, 2010

 

Background: The relationship between common genetic polymorphisms and susceptibility to neurological complications in West Nile virus (WNV) infected individuals is not well understood.

Methods: From 2003 to 2008 patients meeting case definitions for severe WNV disease (meningitis, encephalitis, or acute flaccid paralysis) from Canada and U.S were compared to WNV infected patients without severe disease. Whole blood samples were collected for genotyping using whole genome screening with the Illumina HumanNS-12 Infinium assay. This included 13,371 single nucleotide polymorphisms (SNPs) which were mostly non-synonymous variants but also included synonymous, UTR, and tag-SNPs. To validate association results from the primary analysis, a panel of 34 SNPs was designed using Sequenom MassARRAY IPLEX Gold including tag SNPs from the primary gene of interest, top 12 SNPs from the primary analysis.

Results: 445 neuroinvasive cases and 813 controls were compared in the primary analysis. SNPs of importance based on statistical significance and biological plausibility included RFC1 (replication factor) (rs2066786) p= 1.67 x 10-6, OR 1.5 (95%CI 1.21 to 1.86); SCN1A (sodium channel, neuronal type 1 alpha subunit) (rs2298771), p= 1.73 x 10-6, OR 1.50 (1.21 to 1.86); and ANPEP (ananyl aminopeptidase) (rs25651) p = 1.73 x 10-4. Replication samples from 617 patients (277 cases and 340 controls) were obtained. Although there was an overall lack of significance in the replication cohort (p > 0.5 for all three SNPs), RFC1- rs2066786 did replicate in the cohort from one state (Nebraska). Joint analysis showed for RFC1 -rs2066786 p= 3.0 x 10 10-5; SCN1A- rs2298771 p= 1.4 x 10-3; and ANPEP- rs25651 p= 3.1 x 10-3. SNPs in other candidate genes (OAS, TLR3) were not significant.

Conclusion: Novel genetic variants may play a role in susceptibility to severe WNV disease.


Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

Speakers:
Mark Loeb, MD , McMaster University, Hamilton, ON, Canada
Sasha Eskandarian, MSc , McMaster University, Hamilton, ON, Canada
Mark Rupp, MD , University of Nebraska Medical Center, Omaha, NE
Neil Fishman, MD , University of Pennsylvania Medical Center, Philadelphia, PA
Leanne Gasink, MD , Hospital of the University of Pennsylvania, Philadelphia, PA
Jan Patterson, MD , University of Texas Health Science Center San Antonio and South Texas VA, San Antonio, TX
Jonathan Bramson, PhD , McMaster University, Hamilton, ON, Canada
Tom Hudson, MD , Ontario Institute for Cancer Research, Toronto, ON, Canada
Mathieu Lemire, PhD , Ontario Institute for Cancer Research, Toronto, ON, Canada

Disclosures:

M. Loeb, None

S. Eskandarian, None

M. Rupp, None

N. Fishman, None

L. Gasink, None

J. Patterson, None

J. Bramson, None

T. Hudson, None

M. Lemire, None

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