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San Sebastián de los Reyes, Spain

Alcina A.,Institute Parasitologia y Biomedicina Lopez Neyra | Vandenbroeck K.,University of the Basque Country | Vandenbroeck K.,Ikerbasque | Otaegui D.,Institute Investigacion Sanitaria BIODONOSTIA | And 19 more authors.
Genes and Immunity | Year: 2010

Genome-wide association studies (GWAS) have revealed that different diseases share susceptibility variants. Twelve single-nucleotide polymorphisms (SNPs) previously associated with different immune-mediated diseases in GWAS were genotyped in a Caucasian Spanish population of 2864 multiple sclerosis (MS) patients and 2930 controls. Three SNPs were found to be associated with MS: rs1678542 in KIF5A (P0.001, odds ratio (OR)1.13, 95% confidence interval (CI)1.05-1.23); rs3184504 in SH2B3 (P0.00001, OR1.19, 95% CI1.10-1.27) and rs763361 in CD226 (P0.00007, OR1.16, 95%CI1.08-1.25). These variants have previously been associated with rheumatoid arthritis and type 1 diabetes. The SH2B3 polymorphism has additionally been associated with systemic lupus erythematosus. Our results, in addition to validating some of these loci as risk factors for MS, are consistent with shared genetic mechanisms underlying different immune-mediated diseases. These data may help to shape the contribution of each pathway to different disorders. © 2010 Macmillan Publishers Limited All rights reserved. Source


Swaminathan B.,University of the Basque Country | Matesanz F.,Institute Parasitologia y Biomedicina Lopez Neyra | Cavanillas M.L.,Hospital Clinico S. Carlos | Alloza I.,University of the Basque Country | And 10 more authors.
Journal of Neuroimmunology | Year: 2010

A recent meta-analysis of genome-wide association screens coupled to a replication exercise in a combined US/UK collection led to the identification of 4 single nucleotide polymorphisms (SNPs) in three gene loci, i.e. TNFRSF1A, CD6 and IRF8, as novel risk factors for multiple sclerosis with genome-wide level of significance. In the present study, using a combined all-Spain collection of 2515 MS patients and 2942 healthy controls, we demonstrate significant association of rs17824933 in CD6 (P CMH=0.004; OR=1.14; 95% CI 1.04-1.24) and of rs1860545 in TNFRSF1A (P CMH=0.001; OR=1.15; 95% CI 1.06-1.25) with MS, while the low-frequency coding non-synonymous SNP rs4149584 in TNFRSF1A displayed a trend for association (P CMH=0.062; OR=1.27; 95% CI 0.99-1.63). This data reinforce a generic role for CD6 and TNFRSF1A in susceptibility to MS, extending to populations of southern European ancestry. © 2010 Elsevier B.V. Source


Llop S.,Centro Superior Of Investigacion En Salud Publica Csisp | Llop S.,CIBER ISCIII | Ibarlucea J.,CIBER ISCIII | Ibarlucea J.,Institute Investigacion Sanitaria BIODONOSTIA | And 5 more authors.
Gaceta Sanitaria | Year: 2013

Exposure to high levels of mercury during vulnerable periods (such as pregnancy and childhood) may have serious consequences for cognitive development, as observed after acute poisoning episodes in Japan and Irak. The main source of mercury exposure in the general population is consumption of certain types of fish. There is growing concern about the possible neurotoxic effects of mercury, especially in younger children in populations where fish intake is moderate to high. The scientific evidence to date is inconclusive. In Spain, the Childhood and Environment (Infancia y Medio Ambiente [INMA]) project has provided information on levels of prenatal exposure to mercury among 1800 newborns from Valencia, Sabadell, Asturias and Guipúzcoa. In general, levels were high, being above the World Health Organization's recommended dose in 24% of children and above the recommended levels of the U.S. Environmental Protection Agency in 64%. However, the results did not indicate a significant association between prenatal mercury exposure and delayed cognitive development during the second year of life. Various agencies have developed recommendations on fish consumption for pregnant women and children, due to the presence of mercury. These recommendations should be strengthened, since there is general consensus among all regional and national public administrations that fish is an essential source of nutrients for development in the early stages of life. © 2012 SESPAS. Source


Vandenbroeck K.,University of the Basque Country | Vandenbroeck K.,Ikerbasque | Alloza I.,University of the Basque Country | Swaminathan B.,University of the Basque Country | And 11 more authors.
Genes and Immunity | Year: 2011

In recent reports, IRF5 polymorphisms showed significant association with multiple sclerosis (MS) susceptibility in three studied populations and Irf5-deficient mice exhibited an increased susceptibility to viral infection, linked to a significant decrease in the induction of serum type I interferon (IFN). In the present study, we evaluated the association of two IRF5 polymorphisms with MS predisposition and we also addressed whether these polymorphisms were associated with active replication of human herpes virus-6 (HHV-6) observed in a subgroup of MS patients, and/or with response to IFN-β therapy. A total of 1494 MS patients and 1506 ethnically matched controls were genotyped for rs4728142 and rs3807306 with TaqMan pre-designed assays. One hundred and six patients were classified as responders to IFN-β therapy (no relapses/increases in EDSS over the 2-year follow-up) and 112 as non-responders (at least two relapses or an increase in expanded disability status scale (EDSS) of at least one point during the same period). The combined analysis of available datasets yielded an effect size on MS with odds ratio (OR) MantelHaenszel 1.14 (P<0.002) for the IRF5 polymorphisms rs4728142 and rs3807306. Additionally, trends for association were observed between rs3807306T and infection with HHV-6 p0.05, OR (95% CI)1.56 (1.00-2.44) and response to IFN-β therapy P0.09, OR (95% CI)1.39 (0.95-2.05). © 2011 Macmillan Publishers Limited All rights reserved. Source


Alloza I.,University of the Basque Country | Otaegui D.,Institute Investigacion Sanitaria BIODONOSTIA | De Lapuente A.L.,University of the Basque Country | Antiguedad A.,Servicio de Neurologia | And 18 more authors.
Genes and Immunity | Year: 2012

Multiple sclerosis (MS) shares some risk genes with other disorders hallmarked by an autoimmune pathogenesis, most notably IL2RA and CLEC16A. We analyzed 10 single-nucleotide polymorphisms (SNPs) in nine risk genes, which recently emerged from a series of non-MS genome-wide association studies (GWAS), in a Spanish cohort comprising 2895 MS patients and 2942 controls. We identified two SNPs associated with MS. The first SNP, rs6859219, located in ANKRD55 (Chr5), was recently discovered in a meta-analysis of GWAS on rheumatoid arthritis (RA), and emerged from this study with genome-wide significance (odds ratio (OR)=1.35; P=2.3 × 10 -9). The second SNP, rs12785878, is located near DHCR7 (Chr11), a genetic determinant of vitamin D insufficiency, and showed a size effect in MS similar to that recently observed in Type 1 diabetes (T1D; OR=1.10; P=0.009). ANKRD55 is a gene of unknown function, and is flanked proximally by the IL6ST-IL31RA gene cluster. However, rs6859219 did not show correlation with a series of haplotype-tagging SNPs covering IL6ST-IL31RA, analyzed in a subset of our dataset (D′ < 0.31; r 2 < 0.011). Our results expand the number of risk genes shared between MS, RA and T1D. © 2012 Macmillan Publishers Limited All rights reserved. Source

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