HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity
Abstract Background Human leukocyte antigen (HLA)-A*03, hemochromatosis ancestral haplotype marker, was associated with greater iron overload in hemochromatosis cohorts reported before discovery of the HFE gene. We sought to learn whether an A*03-linked locus influences phenotypes in referred HFE p....
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-06-01
|
| Series: | Hereditas |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41065-022-00237-w |
| _version_ | 1818207451459092480 |
|---|---|
| author | James C. Barton J. Clayborn Barton Ronald T. Acton |
| author_facet | James C. Barton J. Clayborn Barton Ronald T. Acton |
| author_sort | James C. Barton |
| collection | DOAJ |
| description | Abstract Background Human leukocyte antigen (HLA)-A*03, hemochromatosis ancestral haplotype marker, was associated with greater iron overload in hemochromatosis cohorts reported before discovery of the HFE gene. We sought to learn whether an A*03-linked locus influences phenotypes in referred HFE p.C282Y homozygotes. Methods We tabulated these phenotypes in probands with p.C282Y homozygosity: age, transferrin saturation (TS), serum ferritin (SF), conditions related to iron overload, fibrosis-four variables (FIB-4) index and aspartate aminotransferase-to-platelet ratio index (APRI) predictors of severe hepatic fibrosis, and iron removed to achieve depletion (QFe/age). We analyzed phenotypes of men and women separately across three A*03 subgroups. Results There were 104 men (57.8%) and 76 women (42.2%). Mean age (SD) was 49 ± 13 y. Mean TS was 79 ± 17%. Median SF (range) was 715 µg/L (28, 6103). Related conditions included: hemochromatosis arthropathy (21.7%); type 2 diabetes (18.9%); hypogonadotropic hypogonadism (5.8% of men); cardiomyopathy (0%); and cirrhosis (10.0%). Median QFe/age was 61 mg/y (0, 714). A*03 homozygosity, heterozygosity, and no A*03 occurred in 37 (20.6%), 104 (57.8%), and 39 probands (21.7%), respectively. In men, mean TS and median SF were significantly higher in A*03 homozygotes than heterozygotes but not A*03-negative probands. In men, median APRI was significantly lower in A*03 heterozygotes than homozygotes and A*03-negative probands. No other phenotypes, including QFe/age, differed significantly across A*03 subgroups in either men or women. Conclusions Our results suggest that an A*03-linked locus does not influence phenotypes in referred HFE p.C282Y homozygotes. It is unlikely that heritable factors that modify phenotypes of p.C282Y homozygotes are linked to the hemochromatosis ancestral haplotype. |
| first_indexed | 2024-12-12T04:29:08Z |
| format | Article |
| id | doaj.art-6d7ed3a5e6e54341b1680e4979fd4d18 |
| institution | Directory Open Access Journal |
| issn | 1601-5223 |
| language | English |
| last_indexed | 2024-12-12T04:29:08Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditas |
| spelling | doaj.art-6d7ed3a5e6e54341b1680e4979fd4d182022-12-22T00:38:08ZengBMCHereditas1601-52232022-06-01159111110.1186/s41065-022-00237-wHLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosityJames C. Barton0J. Clayborn Barton1Ronald T. Acton2Southern Iron Disorders CenterSouthern Iron Disorders CenterSouthern Iron Disorders CenterAbstract Background Human leukocyte antigen (HLA)-A*03, hemochromatosis ancestral haplotype marker, was associated with greater iron overload in hemochromatosis cohorts reported before discovery of the HFE gene. We sought to learn whether an A*03-linked locus influences phenotypes in referred HFE p.C282Y homozygotes. Methods We tabulated these phenotypes in probands with p.C282Y homozygosity: age, transferrin saturation (TS), serum ferritin (SF), conditions related to iron overload, fibrosis-four variables (FIB-4) index and aspartate aminotransferase-to-platelet ratio index (APRI) predictors of severe hepatic fibrosis, and iron removed to achieve depletion (QFe/age). We analyzed phenotypes of men and women separately across three A*03 subgroups. Results There were 104 men (57.8%) and 76 women (42.2%). Mean age (SD) was 49 ± 13 y. Mean TS was 79 ± 17%. Median SF (range) was 715 µg/L (28, 6103). Related conditions included: hemochromatosis arthropathy (21.7%); type 2 diabetes (18.9%); hypogonadotropic hypogonadism (5.8% of men); cardiomyopathy (0%); and cirrhosis (10.0%). Median QFe/age was 61 mg/y (0, 714). A*03 homozygosity, heterozygosity, and no A*03 occurred in 37 (20.6%), 104 (57.8%), and 39 probands (21.7%), respectively. In men, mean TS and median SF were significantly higher in A*03 homozygotes than heterozygotes but not A*03-negative probands. In men, median APRI was significantly lower in A*03 heterozygotes than homozygotes and A*03-negative probands. No other phenotypes, including QFe/age, differed significantly across A*03 subgroups in either men or women. Conclusions Our results suggest that an A*03-linked locus does not influence phenotypes in referred HFE p.C282Y homozygotes. It is unlikely that heritable factors that modify phenotypes of p.C282Y homozygotes are linked to the hemochromatosis ancestral haplotype.https://doi.org/10.1186/s41065-022-00237-wAncestral haplotypeAPRIFIB-4HaplotypeIron overload |
| spellingShingle | James C. Barton J. Clayborn Barton Ronald T. Acton HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity Hereditas Ancestral haplotype APRI FIB-4 Haplotype Iron overload |
| title | HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity |
| title_full | HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity |
| title_fullStr | HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity |
| title_full_unstemmed | HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity |
| title_short | HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity |
| title_sort | hla a 03 the hemochromatosis ancestral haplotype and phenotypes of referred hemochromatosis probands with hfe p c282y homozygosity |
| topic | Ancestral haplotype APRI FIB-4 Haplotype Iron overload |
| url | https://doi.org/10.1186/s41065-022-00237-w |
| work_keys_str_mv | AT jamescbarton hlaa03thehemochromatosisancestralhaplotypeandphenotypesofreferredhemochromatosisprobandswithhfepc282yhomozygosity AT jclaybornbarton hlaa03thehemochromatosisancestralhaplotypeandphenotypesofreferredhemochromatosisprobandswithhfepc282yhomozygosity AT ronaldtacton hlaa03thehemochromatosisancestralhaplotypeandphenotypesofreferredhemochromatosisprobandswithhfepc282yhomozygosity |