title: Genetic variants and susceptibility to neurological complications following West Nile virus infection.
abstract: To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10(-5); odds ratio [OR], 0.68 [95% confidence interval {CI}, .56-.81]); rs2298771 in SCN1A (sodium channel, neuronal type I α subunit) (P = 5.87 × 10(-5); OR, 1.47 [95% CI, 1.21-1.77]); and rs25651 in ANPEP (ananyl aminopeptidase) (P = 1.44 × 10(-4); OR, 0.69 [95% CI, .56-.83]). Additional genotyping of these SNPs in a separate sample of 264 case patients and 296 control patients resulted in a lack of significance in the replication cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P = .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did not identify genetic variants associated with neuroinvasive disease.
authors: Department of Medicine, Clinical Epidemiology, and Biostatistics, McMaster University, Hamilton, Ontario. loebm@mcmaster.ca
authors: Mark
authors: M
authors: Loeb
authors: Sasha
authors: S
authors: Eskandarian
authors: Mark
authors: M
authors: Rupp
authors: Neil
authors: N
authors: Fishman
authors: Leanne
authors: L
authors: Gasink
authors: Jan
authors: J
authors: Patterson
authors: Jonathan
authors: J
authors: Bramson
authors: Thomas J
authors: TJ
authors: Hudson
authors: Mathieu
authors: M
authors: Lemire
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D018826:CD13 Antigens / Q000235:genetics; D016022:Case-Control Studies; D018792:Encephalitis, Viral / Q000235:genetics* / Q000821:virology; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008587:Meningitis, Viral / Q000235:genetics* / Q000821:virology; D008875:Middle Aged; D005810:Multigene Family; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D010243:Paralysis / Q000235:genetics* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019713:Receptors, CCR5 / Q000235:genetics; D051818:Replication Protein C / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D014901:West Nile Fever / Q000150:complications / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C081632:RFC1 protein, human; D019713:Receptors, CCR5; C568242:SCN1A protein, human; D015222:Sodium Channels; D015088:2',5'-Oligoadenylate Synthetase; D018826:CD13 Antigens; D051818:Replication Protein C