GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes.
Pubmed ID: 27936396
Pubmed Central ID: PMC5629344
Journal: Blood cells, molecules & diseases
Publication Date: 03/01/2017
Affiliation: Department of Epidemiology, University of California, Irvine, CA 92697, USA.
MeSH Terms: Humans, Male, Adult, Female, Aged, Homozygote, Age Factors, Middle Aged, Alcohol Drinking, Iron, Mutation, Missense, Acyltransferases, Hemochromatosis Protein
Grants: P30 CA062203, R24 DK093433, R24 DK099846, R01 DK090257, U54 DK110858
Authors: McLaren CE, McLaren GD, Emond MJ, Subramaniam VN, Phatak PD, Barton JC, Adams PC, Powell LW, Gurrin LC, Allen KJ, Ramm GA, Anderson GJ, Chen WP, Phillips JD, Parker CJ
Cite As: Barton JC, Chen WP, Emond MJ, Phatak PD, Subramaniam VN, Adams PC, Gurrin LC, Anderson GJ, Ramm GA, Powell LW, Allen KJ, Phillips JD, Parker CJ, McLaren GD, McLaren CE. GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes. Blood Cells Mol Dis 2017 Mar;63:15-20. Epub 2016 Nov 12.
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 >2247pmol/L (>1000μg/L) and either hepatic iron >236μmol/g dry weight or iron >10g by induction phlebotomy (men and women). We defined normal or mildly elevated iron stores as serum ferritin <674.1pmol/L (<300μg/L) or either age≥40y with iron ≤2.5g iron by induction phlebotomy or age≥50y with ≤3.0g 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.