GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes

Barton, James C., Chen, Wen-pin, Emond, Mary J., Phatak, Pradyumna D., Subramaniam, V. Nathan, Adams, Paul C., Gurrin, Lyle C., Anderson, Gregory J., Ramm, Grant A., Powell, Lawrie W., Allen, Katrina J., Phillips, John D., Parker, Charles J., McLaren, Gordon D. and McLaren, Christine E. (2017) GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes. Blood Cells, Molecules and Diseases, 63 15-20. doi:10.1016/j.bcmd.2016.11.009

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author Barton, James C.
Chen, Wen-pin
Emond, Mary J.
Phatak, Pradyumna D.
Subramaniam, V. Nathan
Adams, Paul C.
Gurrin, Lyle C.
Anderson, Gregory J.
Ramm, Grant A.
Powell, Lawrie W.
Allen, Katrina J.
Phillips, John D.
Parker, Charles J.
McLaren, Gordon D.
McLaren, Christine E.
Title GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes
Formatted title
GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes
Journal name Blood Cells, Molecules and Diseases   Check publisher's open access policy
ISSN 1096-0961
1079-9796
Publication date 2017-03-01
Sub-type Article (original research)
DOI 10.1016/j.bcmd.2016.11.009
Open Access Status File (Author Post-print)
Volume 63
Start page 15
End page 20
Total pages 6
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Collection year 2017
Language eng
Formatted abstract
Background: GNPAT p.D519G positivity is significantly increased in HFE p.C282Y homozygotes with markedly increased iron stores. We sought to determine associations of p.D519G and iron-related variables with iron stores in p.C282Y homozygotes.

Methods: We defined markedly increased iron stores as serum ferritin > 2247 pmol/L (> 1000 μg/L) and either hepatic iron > 236 μmol/g dry weight or iron > 10 g by induction phlebotomy (men and women). We defined normal or mildly elevated iron stores as serum ferritin < 674.1 pmol/L (< 300 μg/L) or either age ≥ 40 y with iron ≤ 2.5 g iron by induction phlebotomy or age ≥ 50 y with ≤ 3.0 g iron by induction phlebotomy (men only). We compared participant subgroups using univariate methods. Using multivariable logistic regression, we evaluated associations of markedly increased iron stores with these variables: age; iron supplement use (dichotomous); whole blood units donated; erythrocyte units received as transfusion; daily alcohol consumption, g; and p.D519G positivity (heterozygosity or homozygosity).

Results: The mean age of 56 participants (94.6% men) was 55 ± 10 (SD) y; 41 had markedly increased iron stores. Prevalences of swollen/tender 2nd/3rd metacarpophalangeal joints and elevated aspartate or alanine aminotransferase were significantly greater in participants with markedly increased iron stores. Only participants with markedly increased iron stores had cirrhosis. In multivariable analyses, p.D519G positivity was the only exposure variable significantly associated with markedly increased iron stores (odds ratio 9.9, 95% CI [1.6, 60.3], p = 0.0126).

Conclusions: GNPAT p.D519G is strongly associated with markedly increased iron stores in p.C282Y homozygotes after correction for age, iron-related variables, and alcohol consumption.
Keyword Hemochromatosis
Iron overload
Rs11558492
Rs1800562
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 27 Dec 2016, 10:21:01 EST by System User on behalf of Learning and Research Services (UQ Library)