H63D is an haemochromatosis associated allele

摘要: Editor,—The UK Haemochromatosis Consortium’s report ( Gut 1997; 41 :841–4) questions the importance of H63D allele in hereditary haemochromatosis (HHC). In their commentary, Goldwurm and Powell :855–6) also doubt relevance H63D. However, there is compelling evidence that associated with HHC.1-12 To evaluate association haemochromatosis, one must first recognise C282Y are independent mutations HFE gene. Because mutation so common highly penetrant, homozygous predominates among cases not observed homozygotes. If excludes from analysis homozygotes, then strong HHC becomes apparent. For five large series North America1-5 have been analysed this manner, we found a significant (p=0.000001) twofold “enrichment” H63D, compared random control cases. studies reported Europe,6-10 “enrichment”, which groups roughly twice frequency groups: Borot et al , p=0.003; Jouanolle p=0.00004; Carella p= 0.073; Martinez p=0.000002; Gottschalk p=0.02. When all data Europe America combined, including those Consortium, quite (p < 0.000001). The might depend on fact patients who compound heterozygotes—that is, C282Y/H63D, at risk developing clinically iron overload. Therefore, may question whether itself haemochromatosis. We tested possibility by re-analysing published (combining 10 studies, … Dr Robson (email:krobson{at}hammer.imm.ox.ac.uk).