RESUMO
Most of the published works so far have aimed at finding genes associated with multiple sclerosis (MS) susceptibility. Very few studies have attempted to correlate disease features with DNA variants. In a well-characterized sample (651 patients) representative of multiple sclerosis natural history, we engaged a comprehensive study of the role of human leukocyte antigen (HLA) in the course of the disease. We investigated the role of HLA-DRB1*15 allele in samples stratified according to severity evaluated by the Multiple Sclerosis Severity Score (MSSS), time to reach EDSS 6.0 and disease type. We found that HLA-DRB1*15 genotype does not influence MS severity even among patients presenting with a given type of the disease. However, we show for the first time that HLA-DRB1*15 allele modulates the course of MS for relapsing-remitting (RR) onset patients likely by precipitating the secondary progressive (SP) phase.
Assuntos
Antígenos HLA-DR/genética , Esclerose Múltipla/genética , Esclerose Múltipla/fisiopatologia , Adolescente , Adulto , Criança , Feminino , Antígenos HLA-DR/metabolismo , Cadeias HLA-DRB1 , Humanos , MasculinoRESUMO
Multiple sclerosis (MS) is the most common chronic inflammatory neurologic disorder diagnosed in young adults and, due to its chronic course, is responsible for a substantial economic burden. MS is considered to be a multifactorial disease in which both genetic and environmental factors intervene. The well-established human leukocyte antigen (HLA) association does not completely explain the genetic impact on disease susceptibility. However, identification and validation of non-HLA-genes conferring susceptibility to MS has proven to be difficult probably because of the small individual contribution of each of these genes. Recently, associations with two single nucleotide polymorphisms (SNPs) in the IL2RA gene (rs12722489, rs2104286) and one SNP in the IL7RA gene (rs6897932) have been reported by several groups. These three SNPs were genotyped in a French and a German population of MS patients using the hME assay by the matrix-assisted laser desorption/ionization time of flight technology (Sequenom, San Diego, CA, USA). We show that these SNPs do contribute to the risk of MS in these two unrelated European MS patient populations with odds ratios varying from 1.1 to 1.5. The discovery and validation of new genetic risk factors in independent populations may help toward the understanding of MS pathogenesis by providing valuable information on biological pathways to be investigated.
Assuntos
Predisposição Genética para Doença/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Esclerose Múltipla/genética , Receptores de Interleucina-7/genética , Adulto , Idoso , Feminino , França , Frequência do Gene , Genótipo , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Assisted Reproductive Technologies (ART) are authorized in France in couples infected by the human immunodeficiency virus (HIV) since the French legislation of May 10th, 2001. The goals are to reduce the risk of viral transmission between partners and to treat an underlying infertility. The classical techniques are used: IUI, IVF or ICSI, but all of them must be done in specifically authorized laboratories. ART outcome is favourable when only the man is infected, but seems to be less favourable when the woman is infected. Management of pregnancy planning should first propose to women infected by HIV, self inseminations when possible, and if needed, a quick ART treatment as some studies showed ovarian function alterations in HIV women. When the man is infected, IUI would be first proposed. Thousands of HIV positive male partners have used ART in Europe and no contamination has been reported so far. Approximately half of couples with one or both partners infected can hope to have a child through the ART process.
Assuntos
Infecções por HIV , Técnicas de Reprodução Assistida , Feminino , Humanos , Masculino , Técnicas de Reprodução Assistida/normasRESUMO
A quantimetric study of vaginal superficial cells is done every day of the sexual cycle on five normal women (no pill) with a cervical smear of type 2 (Papanicolaou classification). Our results show that nucelo-cytoplasmic ratio for 98% of the cells varies between 0.0040 and 0.0210. This level is independant of age and cycle duration and is proposed as reference for later studies of women under pill or with cervico-vaginal dysplasia and cancer.