GNPAT variant (D519G) is not associated with an elevated serum ferritin or iron removed by phlebotomy in patients referred for C282Y-linked hemochromatosis

Background. Previous studies in high and low expressors has demonstrated that a variant in the GNPAT gene (D519G, Rs11558492, chromosome 1, exon 11) has been associated with severe iron overload in C282Y homozygotes for hemochromatosis. In this study, a GNPATvariant was assessed prospectively in patients referred for HFE testing over a range of serum ferritin levels.Material and methods. Consecutive patients sent for HFE testing were studied for the GNPAT variant using a TaqMan kit assay (Life Technologies, Burlington, ON). Serum ferritin and iron removed by phlebotomy was compared in C282Y homozygotes with and without the GNPATvariant. The frequency of the GNPATvariant in referred patients was compared to a control population of voluntary blood donors without HFE mutations.Results. There were 533 patients that had GNPATanalysis. The allele frequency for the GNPATvariant in C282Y homozygotes (n = 75) was 0.226 and in wild type control patients (n = 458) was 0.213 (p = .07). Forty-eight percent (of the C282Y homozygotes were heterozygous (n = 28) or homozygous (n = 8) for the GNPATvariant. The mean (log)ferritin and iron removed did not significantly differ between C282Y homozygous with GNPAT homozygotes, GNPAT heterozygotes, and without the GNPATvariant (p = 0.84).Conclusions. C282Y homozygotes referred for HFE testing commonly have a GNPATvariant. This GNPATvariant does not appear be a co-modifying gene affecting expression of HFE related hemochromatosis in this population. The GNPATvariant does not predict the severity of iron overload