Associations between the presence of specific antibodies to the West Nile Virus infection and candidate genes in Romanian horses from the Danube delta
MOLECULAR BIOLOGY REPORTS
Authors: Stejskalova, K.; Janova, E.; Horecky, C.; Horecka, E.; Vaclavek, P.; Hubalek, Z.; Relling, K.; Cvanova, M.; D'Amico, G.; Mihalca, A. D.; Modry, D.; Knoll, A.; Horin, P.
Abstract
The West Nile virus (WNV) is a mosquito-borne flavivirus causing meningoencephalitis in humans and animals. Due to their particular susceptibility to WNV infection, horses serve as a sentinel species. In a population of Romanian semi-feral horses living in the Danube delta region, we have analyzed the distribution of candidate polymorphic genetic markers between anti WNV-IgG seropositive and seronegative horses. Thirty-six SNPs located in 28 immunity-related genes and 26 microsatellites located in the MHC and LY49 complex genomic regions were genotyped in 57 seropositive and 32 seronegative horses. The most significant association (p(corr)<0.0002) was found for genotypes composed of markers of the SLC11A1 and TLR4 genes. Markers of five other candidate genes (ADAM17, CXCR3, IL12A, MAVS, TNFA), along with 5 MHC class I and LY49-linked microsatellites were also associated with the WNV antibody status in this model horse population. The OAS1 gene, previously associated with WNV-induced clinical disease, was not associated with the presence of anti-WNV antibodies.
A cytokine gene screen uncovers SOCS1 as genetic risk factor for multiple sclerosis
GENES AND IMMUNITY
Authors: Vandenbroeck, K.; Alvarez, J.; Swaminathan, B.; Alloza, I.; Matesanz, F.; Urcelay, E.; Comabella, M.; Alcina, A.; Fedetz, M.; Ortiz, M. A.; Izquierdo, G.; Fernandez, O.; Rodriguez-Ezpeleta, N.; Matute, C.; Caillier, S.; Arroyo, R.; Montalban, X.; Oksenberg, J. R.; Antigueedad, A.; Aransay, A.
Abstract
Cytokine and cytokine receptor genes, including IL2RA, IL7R and IL12A, are known risk factors for multiple sclerosis (MS). Excitotoxic oligodendroglial death mediated by glutamate receptors contributes to demyelinating reactions. In the present study, we screened 368 single-nucleotide polymorphisms (SNPs) in 55 genes or gene clusters coding for cytokines, cytokine receptors, suppressors of cytokine signaling (SOCS), complement factors and glutamate receptors for association with MS in a Spanish Basque resident population. Top-scoring SNPs were found within or nearby the genes coding for SOCS-1 (P = 0.0005), interleukin-28 receptor, alpha chain (P = 0.0008), oncostatin M receptor (P = 0.002) and interleukin-22 receptor, alpha 2 (IL22RA2; P = 0.003). The SOCS1 rs243324 variant was validated as risk factor for MS in a separate cohort of 3919 MS patients and 4003 controls (combined Cochran-Mantel-Haenszel P = 0.00006; odds ratio (OR) = 1.13; 95% confidence interval (CI) = 1.07-1.20). In addition, the T allele of rs243324 was consistently increased in relapsing-remitting/secondary progressive versus primary-progressive MS patients, in each of the six data sets used in this study (P-CMH = 0.0096; OR = 1.24; 95% Cl 1.05-1.46). The association with SOCS1 appears independent from the chr16MS risk locus CLEC16A. Genes and Immunity (2012) 13, 21-28; doi:10.1038/gene.2011.44; published online 30 June 2011
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