PMID- 37179448
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230606
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 May 13
TI  - The ancestral haplotype markers HLA -A3 and B7 do not influence the likelihood of 
      advanced hepatic fibrosis or cirrhosis in HFE hemochromatosis.
PG  - 7775
LID - 10.1038/s41598-023-35028-4 [doi]
LID - 7775
AB  - Advanced hepatic fibrosis occurs in up to 25% of individuals with C282Y 
      homozygous hemochromatosis. Our aim was to determine whether human leukocyte 
      antigen (HLA)-A3 and B7 alleles act as genetic modifiers of the likelihood of 
      advanced hepatic fibrosis. Between 1972 and 2013, 133 HFE C282Y homozygous 
      individuals underwent clinical and biochemical evaluation, HLA typing, liver 
      biopsy for fibrosis staging and phlebotomy treatment. Hepatic fibrosis was graded 
      according to Scheuer as F0-2 (low grade hepatic fibrosis), F3-4 (advanced hepatic 
      fibrosis), and F4 cirrhosis. We analysed associations between the severity of 
      fibrosis and HLA-A3 homozygosity, heterozygosity or absence, with or without the 
      presence of HLA-B7 using categorical analysis. The mean age of HLA-A3 homozygotes 
      (n = 24), heterozygotes (n = 65) and HLA-A3 null individuals (n = 44) was 
      40 years. There were no significant differences between the groups for 
      mean(+/- SEM) serum ferritin levels (1320 +/- 296, 1217 +/- 124, 1348 +/- 188 [Formula: 
      see text]g/L), hepatic iron concentration (178 +/- 26, 213 +/- 22, 199 +/- 29 [Formula: 
      see text]mol/g), mobilizable iron stores (9.9 +/- 1.5, 9.5 +/- 1.5, 11.5 +/- 1.7 g iron 
      removed via phlebotomy), frequency of advanced hepatic fibrosis (5/24[12%], 
      13/63[19%], 10/42[19%]) or cirrhosis (3/24[21%], 12/63[21%], 4/42[24%]), 
      respectively. The presence or absence of HLA-B7 did not influence the outcome. 
      Thus, HLA-A3 and HLA-B7 alleles are not associated with the risk of advanced 
      hepatic fibrosis or cirrhosis in C282Y hemochromatosis.
CI  - (c) 2023. The Author(s).
FAU - Olynyk, John K
AU  - Olynyk JK
AD  - Medical School, Curtin University, Bentley, WA, Australia. 
      john.olynyk@health.wa.gov.au.
AD  - Department of Gastroenterology, Fiona Stanley Fremantle Hospital Group, Murdoch, 
      WA, Australia. john.olynyk@health.wa.gov.au.
FAU - Grainger, Richard
AU  - Grainger R
AD  - Department of Gastroenterology, Fiona Stanley Fremantle Hospital Group, Murdoch, 
      WA, Australia.
FAU - Currie, Helen
AU  - Currie H
AD  - Department of Gastroenterology, Fiona Stanley Fremantle Hospital Group, Murdoch, 
      WA, Australia.
FAU - Ramm, Louise E
AU  - Ramm LE
AD  - QIMR-Berghofer Medical Research Institute, Herston, QLD, Australia.
AD  - Faculty of Medicine, The University of Queensland, Herston, QLD, Australia.
FAU - Ramm, Grant A
AU  - Ramm GA
AD  - QIMR-Berghofer Medical Research Institute, Herston, QLD, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230513
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (HLA-A3 Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (Hemochromatosis Protein)
RN  - E1UOL152H7 (Iron)
RN  - 0 (HLA Antigens)
RN  - 0 (HFE protein, human)
SB  - IM
MH  - Humans
MH  - *Hemochromatosis/genetics/pathology
MH  - HLA-A3 Antigen/genetics
MH  - Haplotypes
MH  - Histocompatibility Antigens Class I/genetics
MH  - HLA-B7 Antigen/genetics
MH  - Hemochromatosis Protein/genetics
MH  - Liver Cirrhosis/genetics/pathology
MH  - Iron
MH  - Homozygote
MH  - HLA Antigens/genetics
PMC - PMC10183001
COIS- The authors declare no competing interests.
EDAT- 2023/05/14 01:07
MHDA- 2023/05/15 11:42
PMCR- 2023/05/13
CRDT- 2023/05/13 23:23
PHST- 2022/12/16 00:00 [received]
PHST- 2023/05/11 00:00 [accepted]
PHST- 2023/05/15 11:42 [medline]
PHST- 2023/05/14 01:07 [pubmed]
PHST- 2023/05/13 23:23 [entrez]
PHST- 2023/05/13 00:00 [pmc-release]
AID - 10.1038/s41598-023-35028-4 [pii]
AID - 35028 [pii]
AID - 10.1038/s41598-023-35028-4 [doi]
PST - epublish
SO  - Sci Rep. 2023 May 13;13(1):7775. doi: 10.1038/s41598-023-35028-4.