Reduced phenotypic expression in genetic hemochromatosis with time: Role of exposure to non-genetic modifiers.
J Hepatol
; 70(1): 118-125, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30244162
ABSTRACT
BACKGROUND & AIMS:
Genetic hemochromatosis is mainly related to the homozygous p.Cys282Tyr (C282Y) mutation in the HFE gene, which causes hepcidin deficiency. Its low penetrance suggests the involvement of cofactors that modulate its expression. We aimed to describe the evolution of disease presentation and of non-genetic factors liable to impact hepcidin production in the long term.METHODS:
Clinical symptoms, markers of iron load, and risk factors according to the year of diagnosis were recorded over 30â¯years in a cohort of adult C282Y homozygotes. A total of 2,050 patients (1,460 probands [804 males and 656 females] and 542 relatives [244 males and 346 females]) were studied.RESULTS:
Over time (i) the proband-to-relative ratio remained roughly stable; (ii) the gender ratio tended towards equilibrium among probands; (iii) age at diagnosis did not change among males and increased among females; (iv) the frequency of diabetes and hepatic fibrosis steadily decreased while that of chronic fatigue and distal joint symptoms remained stable; (v) transferrin saturation, serum ferritin and the amount of iron removed decreased; and (vi) the prevalence of excessive alcohol consumption decreased while that of patients who were overweight increased. Tobacco smoking was associated with increased transferrin saturation.CONCLUSION:
Genetic testing did not alter the age at diagnosis, which contrasts with the dramatic decrease in iron load in both genders. Tobacco smoking could be involved in the extent of iron loading. Besides HFE testing, which enables the diagnosis of minor forms of the disease, the reduction of alcohol consumption and the increased frequency of overweight patients may have played a role in the decreased long-term iron load, as these factors are likely to improve hepcidin production. LAYSUMMARY:
Genetic hemochromatosis is an inherited disorder that leads to progressive iron overload in the body. It results in chronic fatigue and in potential liver (cirrhosis), pancreas (diabetes) and joint (arthritis) damage in adulthood. The present study showed that tobacco smoking may aggravate iron loading, but that hemochromatosis has become less and less severe over the last 30â¯years despite patients being older at diagnosis, likely because of the protective effects of lower alcohol consumption and of increased weight in the French population.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína da Hemocromatose
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Hemocromatose
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Mutação
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article