RESUMO
Multiple sclerosis (MS) is a chronic neuroinflammatory autoimmune disease believed to arise from complex interactions of both environmental and genetic factors. As in other complex diseases with autoimmune features, a genetic association with the human leukocyte antigen (HLA) complex is well documented. Association and genome-wide studies were performed in Portuguese patients with MS over several years. Genes such as HLA-DRB1, HLA-A, HFE, TNFA, CTLA-4, PTPN22 and ApoE were investigated. ApoE, PTPN22 1858T, CTLA-4 -318C, TNFA-308A, HFE C282Y and TLR9 T-1237C polymorphisms were not shown to be associated with the development of MS. The HLA-DRB1*15 allele was confirmed as the major genetic marker for susceptibility to MS. The presence of HLA-A*02 and TNFA -238A alleles decreased the risk of developing MS. Patients carrying the HFE C282Y variant seem to have a worse prognosis. The HLA-DRB1*15 and PTPN22 1858T variants were associated with a better outcome in this population.
Assuntos
Esclerose Múltipla/genética , Estudos de Associação Genética , Antígenos HLA/genética , Humanos , PortugalRESUMO
Genetic factors are known to influence susceptibility to multiple sclerosis (MS) but the genes involved are largely undefined. Here, we report an association study based on 200 patients and 200 controls from the Porto region in Portugal. A total of 3974 markers were successfully typed from which we have identified 46 markers showing evidence of association. When compared to a physical map three regions were found with two of these markers less than 1.5 Mb apart: chromosomes 6p21.3 (the MHC region), 6q14.1 and 7q34.
Assuntos
Predisposição Genética para Doença , Testes Genéticos/métodos , Genoma Humano , Esclerose Múltipla/genética , Adolescente , Idoso , Estudos de Casos e Controles , DNA/sangue , Eletroforese Capilar , Feminino , Testes Genéticos/estatística & dados numéricos , Genética Populacional , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Reação em Cadeia da Polimerase , Portugal/epidemiologiaRESUMO
Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a genetic component. Until now, the more consistent association with the disease is found with the major histocompatibility complex, especially HLA-DRB1*1501-DQB1*0602 haplotype. In this report, we demonstrate the interaction of Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4 [CD152]) gene with DRB1*15 haplotype in multiple sclerosis genetic susceptibility. Our data were obtained from two European independent family-based studies including 610 multiple sclerosis family trios. Ann Neurol 2003;54:119-122
