Genetics of hereditary hemochromatosis : a clinical perspective

E.K. Gan, Debbie Trinder, O.T. Ayonrinde, John Olynyk

    Research output: Contribution to journalArticle

    2 Citations (Scopus)

    Abstract

    Hereditary hemochromatosis due to homozygosity for the C282Y mutation in the HFE gene product is the most common autosomal recessive genetic disorder in populations of northern European descent, where it attains a maximum prevalence of approximately one in 200. Cross-sectional and longitudinal studies have revealed that clinically significant iron-overload disease develops in at least 28% of male and 1% of female HFE C282Y homozygotes. The relatively low clinical penetrance is largely unexplained. Current evidence suggests a limited role for digenic inheritance of mutations in iron homeostasis genes in modifying the penetrance of hemochromatosis. Male gender is a strong genetic factor, promoting expression of clinical disease. Dietary intake of alcohol and noncitrus fruit may also act as important environmental modifiers of penetrance. With genetic analyses becoming simpler to perform, new genetic modifiers of hepatic iron loading and liver fibrogenesis are likely to be forthcoming.
    Original languageEnglish
    Pages (from-to)225-239
    JournalExpert review of endocrinology & metabolism
    Volume4
    Issue number3
    DOIs
    Publication statusPublished - 2009

    Fingerprint

    Hemochromatosis
    Penetrance
    Iron
    Mutation
    Inborn Genetic Diseases
    Iron Overload
    Liver
    Homozygote
    Genes
    Longitudinal Studies
    Fruit
    Homeostasis
    Cross-Sectional Studies
    Alcohols
    Population

    Cite this

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    abstract = "Hereditary hemochromatosis due to homozygosity for the C282Y mutation in the HFE gene product is the most common autosomal recessive genetic disorder in populations of northern European descent, where it attains a maximum prevalence of approximately one in 200. Cross-sectional and longitudinal studies have revealed that clinically significant iron-overload disease develops in at least 28{\%} of male and 1{\%} of female HFE C282Y homozygotes. The relatively low clinical penetrance is largely unexplained. Current evidence suggests a limited role for digenic inheritance of mutations in iron homeostasis genes in modifying the penetrance of hemochromatosis. Male gender is a strong genetic factor, promoting expression of clinical disease. Dietary intake of alcohol and noncitrus fruit may also act as important environmental modifiers of penetrance. With genetic analyses becoming simpler to perform, new genetic modifiers of hepatic iron loading and liver fibrogenesis are likely to be forthcoming.",
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    Genetics of hereditary hemochromatosis : a clinical perspective. / Gan, E.K.; Trinder, Debbie; Ayonrinde, O.T.; Olynyk, John.

    In: Expert review of endocrinology & metabolism, Vol. 4, No. 3, 2009, p. 225-239.

    Research output: Contribution to journalArticle

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    T1 - Genetics of hereditary hemochromatosis : a clinical perspective

    AU - Gan, E.K.

    AU - Trinder, Debbie

    AU - Ayonrinde, O.T.

    AU - Olynyk, John

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    AB - Hereditary hemochromatosis due to homozygosity for the C282Y mutation in the HFE gene product is the most common autosomal recessive genetic disorder in populations of northern European descent, where it attains a maximum prevalence of approximately one in 200. Cross-sectional and longitudinal studies have revealed that clinically significant iron-overload disease develops in at least 28% of male and 1% of female HFE C282Y homozygotes. The relatively low clinical penetrance is largely unexplained. Current evidence suggests a limited role for digenic inheritance of mutations in iron homeostasis genes in modifying the penetrance of hemochromatosis. Male gender is a strong genetic factor, promoting expression of clinical disease. Dietary intake of alcohol and noncitrus fruit may also act as important environmental modifiers of penetrance. With genetic analyses becoming simpler to perform, new genetic modifiers of hepatic iron loading and liver fibrogenesis are likely to be forthcoming.

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