RESUMO
p phenotype individuals lack both P(k) (Gb3) and P (Gb4) glycolipid antigens of the P blood group system. To explore the molecular basis for this phenotype, DNA sequences of Gb3 synthase (alpha1, 4-galactosyltransferase; alpha1,4Gal-T) in six p phenotype individuals from Japan and Sweden were analyzed. A missense mutation P251L and a nonsense mutation W261stop in three and one Japanese indivuiduals, respectively, and missense mutations M183K and G187D in one each of two Swedish p individuals were found, indicating that p individuals from Japan and Sweden have distinct and multiple homozygous point mutations in the coding region. In the function analysis of the mutated alpha1,4Gal-Ts by the transfection of the expression vectors, P251L and M183K mutations showed complete loss of enzyme function, and W261stop and G187D mutations resulted in the marginal activity. BLAST analysis of homologous sequences of alpha1, 4Gal-T revealed that three residues, Met(183), Gly(187), and Pro(251), at which missense mutations were found, were highly conserved among all species examined, suggesting their importance for the function of alpha1,4Gal-T.
Assuntos
Galactosiltransferases/genética , Genética Populacional , Mutação de Sentido Incorreto , Sistema do Grupo Sanguíneo P/genética , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , Galactosiltransferases/química , Humanos , Japão , Dados de Sequência Molecular , Fenótipo , Homologia de Sequência de Aminoácidos , SuéciaRESUMO
Thirty six members of a family with symptoms and signs from the skin and/or the joints were examined clinically and radiologically and HLA typed. Fourteen were classified as having inflammatory joint disease, eight of them with more than one disease within the spondylarthropathy group (SpA). Four had psoriasis of the skin, two of whom had psoriatic arthritis. Ten (five males, five females) had radiological signs of sacroiliitis, eight of them fulfilled the criteria for SpA. Five (four males, one female) with sacroiliitis had radiological signs of spine involvement. One female member was classified as having rheumatoid arthritis. Seven with sacroiliitis were HLA-B27 positive, related to the same haplotype. Two with psoriasis were B27 positive and the other two had another haplotype in common. No single HLA antigen or haplotype was associated with the inflammatory joint manifestations or skin lesions. This suggests involvement of other gene loci or coincidence of multicases.
Assuntos
Espondilite Anquilosante/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/genética , Artrite Psoriásica/patologia , Artrite Reativa/genética , Artrite Reativa/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Feminino , Antígenos HLA/genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Pele/patologia , Espondilite Anquilosante/patologiaRESUMO
The HLA-A, B and DR antigens were analyzed with serological methods in 75 patients with polymyalgia rheumatica (PMR). In PMR patients the frequency of the HLA-DR4 antigen was significantly higher (62.1%) compared to blood donors (40%), p < 0.05, but did not differ from patients with seropositive rheumatoid arthritis (RA) from the same area (63.1%). In contrast, the frequency of HLA-B27 in the PMR patients (9.3%) was significantly lower compared to RA (27.2%), p < 0.01, but did not differ from blood donors (16.9%). There was no association between DR4 and disease affliction or severity in PMR. The increased frequency of HLA-B27 in RA but not in PMR in the population of northern Sweden suggests an immunogenetic difference between these two HLA-DR4 associated diseases.