title: Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Multiple Sclerosis.
abstract: Several neurochemical, neuropathological, and experimental data suggest a possible role of oxidative stress in the ethiopathogenesis of multiple sclerosis(MS). Heme-oxygenases(HMOX) are an important defensive mechanism against oxidative stress, and HMOX1 is overexpressed in the brain and spinal cord of MS patients and in experimental autoimmune encephalomyelitis(EAE). We analyzed whether common polymorphisms affecting the HMOX1 and HMOX2 genes are related with the risk to develop MS. We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations(CNVs) of these genes in 292 subjects MS and 533 healthy controls, using TaqMan assays. The frequencies of HMOX2 rs1051308AA genotype and HMOX2 rs1051308A and HMOX1 rs2071746A alleles were higher in MS patients than in controls, although only that of the SNP HMOX2 rs1051308 in men remained as significant after correction for multiple comparisons. None of the studied polymorphisms was related to the age at disease onset or with the MS phenotype. The present study suggests a weak association between HMOX2 rs1051308 polymorphism and the risk to develop MS in Spanish Caucasian men and a trend towards association between the HMOX1 rs2071746A and MS risk.
authors: Department of Pharmacology, University of Extremadura, Cáceres, SPAIN.
authors: José A G
authors: JA
authors: Agúndez
authors: Department of Pharmacology, University of Extremadura, Cáceres, SPAIN.
authors: Elena
authors: E
authors: García-Martín
authors: Department of Pharmacology, University of Extremadura, Badajoz, SPAIN.
authors: Carmen
authors: C
authors: Martínez
authors: CIBERNED,Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, SPAIN.|Service of Neurology, Hospital Universitario Doce de Octubre, Madrid, SPAIN.|Department of Medicine, University Complutense, Madrid, SPAIN.
authors: Julián
authors: J
authors: Benito-León
authors: Section of Neurology, Hospital La Mancha-Centro, Alcázar de San Juan (Ciudad Real), SPAIN.
authors: Jorge
authors: J
authors: Millán-Pascual
authors: Service of Neurology, Hospital Universitario Doce de Octubre, Madrid, SPAIN.|Department of Medicine, University Complutense, Madrid, SPAIN.
authors: María
authors: M
authors: Díaz-Sánchez
authors: Service of Neurology, Hospital Universitario Doce de Octubre, Madrid, SPAIN.|Department of Medicine, University Complutense, Madrid, SPAIN.
authors: Patricia
authors: P
authors: Calleja
authors: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma, Cantoblanco, Madrid, SPAIN.
authors: Diana
authors: D
authors: Pisa
authors: Section of Neurology, Hospital La Mancha-Centro, Alcázar de San Juan (Ciudad Real), SPAIN.
authors: Laura
authors: L
authors: Turpín-Fenoll
authors: Section of Neurology, Hospital La Mancha-Centro, Alcázar de San Juan (Ciudad Real), SPAIN.|Department of Medicine-Neurology, Hospital "Príncipe de Asturias". Universidad de Alcalá, Alcalá de Henares (Madrid), SPAIN.|Section of Neurology, Hospital Universitario del Sureste. Arganda del Rey (Madrid), SPAIN.
authors: Hortensia
authors: H
authors: Alonso-Navarro
authors: CIBERNED,Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, SPAIN.|Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, Universidad de Navarra, Pamplona, SPAIN.|Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, SPAIN.|Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, SPAIN.
authors: Pau
authors: P
authors: Pastor
authors: CIBERNED,Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, SPAIN.|Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, Universidad de Navarra, Pamplona, SPAIN.|Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, SPAIN.
authors: Sara
authors: S
authors: Ortega-Cubero
authors: Department of Medicine-Neurology, Hospital "Príncipe de Asturias". Universidad de Alcalá, Alcalá de Henares (Madrid), SPAIN.
authors: Lucía
authors: L
authors: Ayuso-Peralta
authors: Department of Medicine-Neurology, Hospital "Príncipe de Asturias". Universidad de Alcalá, Alcalá de Henares (Madrid), SPAIN.
authors: Dolores
authors: D
authors: Torrecillas
authors: Department of Medicine-Neurology, Hospital "Príncipe de Asturias". Universidad de Alcalá, Alcalá de Henares (Madrid), SPAIN.
authors: Esteban
authors: E
authors: García-Albea
authors: Section of Neurology, Hospital Universitario del Sureste. Arganda del Rey (Madrid), SPAIN.
authors: José Francisco
authors: JF
authors: Plaza-Nieto
authors: Department of Medicine-Neurology, Hospital "Príncipe de Asturias". Universidad de Alcalá, Alcalá de Henares (Madrid), SPAIN.|Section of Neurology, Hospital Universitario del Sureste. Arganda del Rey (Madrid), SPAIN.
authors: Félix Javier
authors: FJ
authors: Jiménez-Jiménez
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D064368:Healthy Volunteers; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2