1. DRB1*03:01 Haplotypes: Differential Contribution to Multiple Sclerosis Risk and Specific Association with the Presence of Intrathecal IgM Bands
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José C. Álvarez-Cermeño, Luisa M. Villar, M. Carmen Cénit, Rafael Arroyo, Laura Leyva, Elena Urcelay, Concepción Núñez, Oscar Fernandez, Emilio G. de la Concha, María L. Cavanillas, [Concha,E G de la, Cavanillas, ML, Cénit, MC, Ircelay, E, Núñez, C] Department of Clinical Immunology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain. [Arroyo, R] Department of Neurology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain. [Fernández, O] Department of Neurology, Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya, Málaga, Spain. [Álvarez-Cermeño, JC] Department of Neurology, Hospital Ramón y Cajal, Madrid, Spain. [Leyva, L] Research Laboratory. Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya and Fundación IMABIS, Málaga, Spain. [Villar, LM] Department of Immunology, Hospital Ramón y Cajal, Madrid, Spain., and This work was supported by project PI10/1985 from ‘‘Fondo de Investigaciones Sanitarias’’. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Inmunoglobulina M ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Risk Factors ,Factores de Riesgo ,Genetics ,Multidisciplinary ,Cadenas HLA-DRB1 ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings] ,Predisposición genética a la enfermedad ,Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings] ,Humanos ,Neurology ,01 antigen [HLA-DRB1*03] ,Medicine ,Haplotipos ,Research Article ,Multiple Sclerosis ,Science ,Immunology ,Chemicals and Drugs::Biological Factors::Antigens::Isoantigens::Histocompatibility Antigens::HLA Antigens::HLA-D Antigens::HLA-DR Antigens::HLA-DR beta-Chains::HLA-DRB1 Chains [Medical Subject Headings] ,Human leukocyte antigen ,Biology ,Autoimmune Diseases ,Estudios caso-control ,medicine ,Humans ,Diseases::Nervous System Diseases::Demyelinating Diseases::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [Medical Subject Headings] ,Genetic Predisposition to Disease ,Allele ,Risk factor ,Genotyping ,Genetic Association Studies ,Evolutionary Biology ,Population Biology ,Estudios de asociación genética ,Multiple sclerosis ,Haplotype ,Case-control study ,Computational Biology ,Human Genetics ,medicine.disease ,Demyelinating Disorders ,01 [Antigeno HLA-DRB1*03] ,Haplotypes ,Immunoglobulin M ,Esclerosis Múltiple ,Case-Control Studies ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Immunoglobulin Isotypes::Immunoglobulin M [Medical Subject Headings] ,biology.protein ,Clinical Immunology ,Population Genetics ,HLA-DRB1 Chains - Abstract
Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Multiple sclerosis (MS) is a multifactorial disease with a genetic basis. The strongest associations with the disease lie in the Human Leukocyte Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk factor associated to MS so far, no consistent effect has been described for any other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across populations and studies. We postulate that those discrepancies could be due to differences in the diverse haplotypes bearing that allele. Thus, we aimed at studying the association of DRB1*03:01 with MS susceptibility considering this allele globally and stratified by haplotypes. We also evaluated the association with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in cerebrospinal fluid. METHODS Genotyping of HLA-B, -DRB1 and -DQA1 was performed in 1068 MS patients and 624 ethnically matched healthy controls. One hundred and thirty-nine MS patients were classified according to the presence (M+, 58 patients)/absence (M-, 81 patients) of OCMB. Comparisons between groups (MS patients vs. controls and M+ vs. M-) were performed with the chi-square test or the Fisher exact test. RESULTS Association of DRB1*03:01 with MS susceptibility was observed but with different haplotypic contribution, being the ancestral haplotype (AH) 18.2 the one causing the highest risk. Comparisons between M+, M- and controls showed that the AH 18.2 was affecting only M+ individuals, conferring a risk similar to that caused by DRB1*15:01. CONCLUSIONS The diverse DRB1*03:01-containing haplotypes contribute with different risk to MS susceptibility. The AH 18.2 causes the highest risk and affects only to individuals showing OCMB. Yes
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- 2012