Antígenos de histocompatibilidade de classe I em pacientes brasileiros portadores de doença de Graves com ou sem oftalmopatia / Histocompatibility antigens class I in Brazilian patients with Graves' disease with or without eye disease

Os antígenos de histocompatibilidade HLA-B8 e -DR3 säo os mais comumente associados à doença de Graves em várias populaçöes caucasianas estudadas. Näo existem publicaçoes completas sobre a tipagem de antígenos ou alelos HLA na populaçao brasileira com doença de Graves. Neste estudo, avaliamos a freqüência dos antígenos HLA de classe II em pacientes com doença de Graves com ou sem oftalmopatia procedentes do Hospital das Clínicas da FMRP-USP. Foram estudados também 191 controles procedentes da mesma área geográfica. Os antígenos foram tipados utilizando a técnica de microlinfocitotoxicidade dependente de complemento. A análise estatística foi realizada usando o teste exato de Fisher bicaudal. Os resultados mostraram que a especificidade HLA-DR3 estava significativamente aumentada em nossos pacientes, conferindo um risco relativo de 4,17 e uma fraçäo etiológica de 0,42. Por outro lado, observamos também diminuiçäo significante das freqüências das especificidades HLA-DR53 e -DQ3, conferindo risco relativo de 0,24 e 0,12, e fraçäo preventiva de 0,98 e 0,99, respectivamente. Embora a populaçäo brasileira seja bastante miscigenada, este estudo mostra que a especificidade HLA-DR3 também confere suscetibilidade à doença em nossa populaçäo. Além disso, acrescenta que as especificidades HLA-DR53 e -DQ3 podem atuar como fatores de proteçäo ao desenvolvimento da doença. Na presença ou na ausência de oftalmopatia a freqüência dos antígenos de histocompatibilidade estudados foi semelhante.

Predisposición genética para desarrollar diabetes mellitus insulino-dependiente: estudio en población de Santiago y Temuco, Chile / Genetic predisposition for developing insulin-dependent diabetes mellitus: study in population from Santiago and Temuco, Chile

Insulin dependent diabetes mellitus (IDDM) is strongly associated with particular HLA-DQ alpha/beta markers in white population. The heterodimers confirmation composed of a DQ alpha chain with an arginine at residue 52 (Arg52) combined to a DQ beta chain lacking an aspartic acid at residue 57 (non asp57) increase markedly the risk to develop IDDM. To confirm this association, 63 IDDM patients from Santiago de Chile registry, 20 IDDM patients from Temuco registry and 74 unrelated helathy non diabetic control subjects were studied. With polymerase chain reaction (PCR) and sequence specific oligonucleotide probes the individuals were typed for their HLA-DQA1 and DQB1 alleles, their DQA1/DQB1 genotype and heterodimers conformation were compared. In diabetic population both markers Arg52 homocygote and non Asp57 homocygote were increased regard to control subjects (R/R: 0.76 and 0.85 vs 0.33; ND/ND: 0.78 and 0.75 vs 0.50, p<0.05). A high relative risk (RR) was determined for both homocygote markers in IDDM groups.compared. Arg52 DQ alpha (R)/non Asp57 DQ beta (ND) heterodimers were strongly associated with susceptibility to IDDM. A high RR was observed in patients with four susceptibility DQ heterodimers (RR1: 13.7 in IDDM-Santiago and RR2: 18.6 in IDDM-Temuco, p<0.00003). The HLA-DQ alpha/beta markers and their risk heterodimers are increased in our diabetic population and could be considered as susceptibility markers to develop IDDM

HLA y diabetes mellitus insulino-dependiente / HLA and insulin-dependent diabetes mellitus

The propensity of an individual to develop type I (insulin dependent) diabetes mellitus is directly related to specipic HLA clase II proteins, specially those from DR and DQ regions. Genetic susceptibility to insulin dependent diabetes arises from a preestablished conformation of alpha and ß chains of DQ and ß chain of DR. Since the classic demonstration by McDevitt and colleagues that DQ ß chain aspartate at position 57 was protective against the development of the disease, many populations have been surveyed to study the association between the incidence Type I diabetes and determined frequencies of DR and DQ haplotypes. The assocation between these markers and susceptibility to Type I diabetes is well established in caucasians at the present time. However, little information is available for Latin American populations, that share a mixture of european, african and native genes. Our group is studying genetic markers of three Latin American populations (Argentina, Perú and Chile) and their possible association to the different incidence of Type I diabetes mellitus in each country