Asunto(s)
Acidosis Láctica/diagnóstico , Disnea/etiología , Infecciones por VIH/complicaciones , Acidosis Láctica/inducido químicamente , Acidosis Láctica/patología , Adulto , Fármacos Anti-VIH/efectos adversos , Antimetabolitos/efectos adversos , Diagnóstico Diferencial , Didanosina/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/patología , Inhibidores de la Transcriptasa Inversa/efectos adversos , Estavudina/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND & AIMS: Hereditary hemochromatosis is associated with C282Y homozygosity. Some heterozygotes may also present with abnormal iron parameters. However, the precise role of H63D and C282Y mutations in iron overload is poorly understood. We investigated the level of expression of the mutated and unmutated HFE alleles in these heterozygous patients. METHODS: We studied the expression of HFE messenger RNAs in peripheral blood mononuclear cells from 34 heterozygotes using reverse-transcription polymerase chain reaction (PCR) followed by enzymatic digestion or sequence analysis of the PCR products, which allows relative quantification of mutated and unmutated transcripts. HFE proteins were quantified by Western blotting in Epstein-Barr virus-immortalized lymphocyte extracts from 2 C282Y and H63D homozygotes and a compound heterozygote. RESULTS: (187C > G; H63D) mutated transcripts predominated in H63D and compound heterozygotes and the normal transcripts in C282Y heterozygotes. The amount of HFE protein was increased in the H63D homozygotes and the compound heterozygote compared with the C282Y homozygotes. In addition, we found a new mutation at codon 282 (C282S) associated with severe iron overload. CONCLUSIONS: We demonstrate the existence of differential allelic expression of the HFE alleles, suggesting that the (187C > G; H63D) mutation plays a role in the disease expression in H63D heterozygotes, in particular when associated with environmental or host factors.