Re: Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank
Once again we pretend that non-HFE haemochromatosis doesn't exist
Sigh . . . well, they *did* look at some non-HFE genes:
rs8177240 (nearest gene TF)
rs7385804 (nearest gene TRF2)
rs855791 (nearest gene TMPR226)
(the gene assignments in brackets above is from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215164/ , the authors of which note "Five confirmed loci contain genes (TF, TFR2, HFE, TMPRSS6, SLC40A1) . . . . known to affect iron homeostasis." Their Figure 1 is a really nice graph showing the effect of variants of genes affecting iron metabolism on different blood tests commonly done to test iron metabolism.)
Unfortunately, Pilling et al did not consider SLC40A1 variants, some of which have been repeatedly shown to produce a type of genetic hemochromatosis in which transferrin doesn't go up until very late in the disease process. More logical jurisidictions that don't ignore SLC40A1 types of iron overload consider these to be the second most common cause of genetic iron overload after HFE-related iron overload.
The standard approach of the Canadian medical system is to ask: Is your transferrin up?
Answer: no.
Canadian medical system: Well, then you don't have hemochromatosis or any sort of iron overload. Go away.
Doctor asks Canadian researcher: what is the prevalence of SLC40A1-related hemochromatosis in Canada?
Canadian researcher: We don't have any.
Doctor: How do you know we don't have any?
Canadian researcher: We did studies looking for people with iron overload and when we found them, we did gene testing on them. People who had genetic iron overload almost all had HFE-related gene variants. We didn't find SLC40A1 iron overload.
Doctor: How do you look for genetic iron overload?
Canadian researcher: We test transferrin saturation. If transferrin saturation is up, then we test the genes. If it isn't, we don't.
Doctor: Transferrin saturation doesn't go up in SLC40A1 iron overload until very late in the disease. You are eliminating people with SLC40A1 before you do any gene testing, which is why you didn't find them.
Canadian researcher: We wouldn't have found them anyhow, because SLC40A1-related iron overload is extremely rare in Canada.
Doctor: How do you know it is extremely rare?
(repeat conversation ad nauseum until doctor gives up and goes back to reading the European (continental) and USA literature . . . . )
Rapid Response:
Re: Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank
Once again we pretend that non-HFE haemochromatosis doesn't exist
Sigh . . . well, they *did* look at some non-HFE genes:
rs8177240 (nearest gene TF)
rs7385804 (nearest gene TRF2)
rs855791 (nearest gene TMPR226)
(the gene assignments in brackets above is from
Unfortunately, Pilling et al did not consider SLC40A1 variants, some of which have been repeatedly shown to produce a type of genetic hemochromatosis in which transferrin doesn't go up until very late in the disease process. More logical jurisidictions that don't ignore SLC40A1 types of iron overload consider these to be the second most common cause of genetic iron overload after HFE-related iron overload.
The standard approach of the Canadian medical system is to ask: Is your transferrin up?
Answer: no.
Canadian medical system: Well, then you don't have hemochromatosis or any sort of iron overload. Go away.
Doctor asks Canadian researcher: what is the prevalence of SLC40A1-related hemochromatosis in Canada?
Canadian researcher: We don't have any.
Doctor: How do you know we don't have any?
Canadian researcher: We did studies looking for people with iron overload and when we found them, we did gene testing on them. People who had genetic iron overload almost all had HFE-related gene variants. We didn't find SLC40A1 iron overload.
Doctor: How do you look for genetic iron overload?
Canadian researcher: We test transferrin saturation. If transferrin saturation is up, then we test the genes. If it isn't, we don't.
Doctor: Transferrin saturation doesn't go up in SLC40A1 iron overload until very late in the disease. You are eliminating people with SLC40A1 before you do any gene testing, which is why you didn't find them.
Canadian researcher: We wouldn't have found them anyhow, because SLC40A1-related iron overload is extremely rare in Canada.
Doctor: How do you know it is extremely rare?
(repeat conversation ad nauseum until doctor gives up and goes back to reading the European (continental) and USA literature . . . . )
Competing interests: No competing interests