GNPAT p.D519G is independently associated with markedly increased iron stores in HFE p.C282Y homozygotes
| Autor: | Gordon D. McLaren, James C. Barton, Wen-Pin Chen, Gregory J. Anderson, V. Nathan Subramaniam, Paul C. Adams, Lawrie W. Powell, Charles J. Parker, Mary J. Emond, Christine E. McLaren, Lyle C. Gurrin, John D. Phillips, Pradyumna D. Phatak, Katrina J. Allen, Grant A. Ramm |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Cirrhosis Alcohol Drinking Iron medicine.medical_treatment Mutation Missense Iron supplement Article 03 medical and health sciences Internal medicine medicine Increased iron Humans Hemochromatosis Protein Molecular Biology Serum ferritin Hemochromatosis Aged business.industry Homozygote Age Factors Cell Biology Hematology Odds ratio Middle Aged Phlebotomy medicine.disease 030104 developmental biology Endocrinology Hereditary hemochromatosis Molecular Medicine Female business Acyltransferases |
| Zdroj: | Blood Cells, Molecules, and Diseases. 63:15-20 |
| ISSN: | 1079-9796 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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