RESUMO
Over the last decade, advances in genetic technologies have accelerated our understanding of the genetic diversity across individuals and populations. Case-control and population-based studies have led to several thousand genetic associations across a range of phenotypes and traits being unveiled. Despite widespread and successful use of organ transplantation as a curative therapy for organ failure, genetic research has yet to make a major impact on transplantation practice aside from HLA matching. New studies indicate that non-HLA loci, termed minor histocompatibility antigens (mHAs), may play an important role in graft rejection. With several million common and rare polymorphisms observed between any two unrelated individuals, a number of these polymorphisms represent mHAs, and may underpin transplantation rejection. Genetic variation is also recognized as contributing to clinical outcomes including response to immunosuppressants, introducing the possibility of genotype-guided prescribing in the very near future. This review summarizes existing knowledge of the impact of genetics on transplantation outcomes and therapeutic responses, and highlights the translational potential that new genomic knowledge may bring to this field.
Assuntos
Rejeição de Enxerto/genética , Antígenos de Histocompatibilidade Menor/genética , Transplante de Órgãos , Polimorfismo Genético/genética , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , PrognósticoRESUMO
OBJECTIVE: To determine the incidence of significant nocturnal hypoglycemia occurring at home in young children with insulin-dependent diabetes mellitus using conventional therapy. DESIGN: Sixty-one children (aged 2.6 to 8.5 years) were studied on one night, at home, with blood collection occurring at dinner, bedtime/supper, 11 PM, 2 AM, and breakfast, with subsequent laboratory analysis. RESULTS: The proportion of subjects with blood glucose levels less than 64, 55, 45, and 36 mg/dl (3.5, 3.0, 2.5, and 2.0 mmol/L) was 37.8%, 17%, 13%, and 8%, respectively. Nocturnal hypoglycemia was associated with younger age (< 5 years 57% vs 5 to 8.5 years 36%; p < 0.001) and lowered glycosylated hemoglobin levels (HbA1c) with a greater than 50% incidence of hypoglycemia seen in subjects with HbA1c levels of less than 8.5%. The average HbA1c concentration was lower in the hypoglycemic group than in the nonhypoglycemic group (7.8 vs 8.3%; p < 0.02). Nocturnal hypoglycemia occurred with increasing frequency throughout the night in subjects less than 5 years of age (dinner, supper, 11 PM, 2 AM, and breakfast incidences being 0%, 12.5%, 26%, 33%, and 30%, respectively) but not in those older than 5 years. Carbohydrate intake at supper did not prevent subsequent hypoglycemia. Blood glucose levels at 11 PM were poor predictors of subsequent hypoglycemia at 2 AM in either the group as a whole or in the children less than 5 years of age. Symptom recognition of nocturnal hypoglycemia was decreased in younger children (< 5 years (36%) > 5 years (58%)), in those with a lower HbA1c, and when hypoglycemia occurred at breakfast rather than at dinner (0% vs 50%). CONCLUSIONS: The incidence of nocturnal hypoglycemia in young children with insulin-dependent diabetes mellitus receiving conventional therapy is unacceptably high and is increased with lowered age and HbA1c concentration; the condition is often asymptomatic. Early-morning hypoglycemia is poorly predicted by a blood glucose determination at 11 PM and is not prevented by carbohydrate intake at supper. In younger children, blood glucose profiles should include early-morning measurements.