{"id":115,"date":"2023-05-22T09:38:39","date_gmt":"2023-05-22T09:38:39","guid":{"rendered":"https:\/\/sites.exeter.ac.uk\/ironoverload\/?page_id=115"},"modified":"2025-02-01T16:28:09","modified_gmt":"2025-02-01T16:28:09","slug":"other-risk-factors","status":"publish","type":"page","link":"https:\/\/sites.exeter.ac.uk\/ironoverload\/other-risk-factors\/","title":{"rendered":"Other factors modifying risk"},"content":{"rendered":"\n<ul>\n<li><a href=\"#sex\" data-type=\"internal\" data-id=\"#sex\">Sex<\/a><\/li>\n\n\n\n<li><a href=\"#age\" data-type=\"internal\" data-id=\"#age\">Age<\/a><\/li>\n\n\n\n<li><a href=\"#alcohol\" data-type=\"internal\" data-id=\"#alcohol\">Alcohol<\/a><\/li>\n\n\n\n<li><a href=\"#diet\" data-type=\"internal\" data-id=\"#diet\">Diet<\/a><\/li>\n\n\n\n<li><a href=\"#obesity\" data-type=\"internal\" data-id=\"#obesity\">Obesity<\/a><\/li>\n\n\n\n<li><a href=\"#other-genetic-variants\" data-type=\"internal\" data-id=\"#other-genetic-variants\">Other genetic variants<\/a><\/li>\n\n\n\n<li><a href=\"#genetic-background\" data-type=\"internal\" data-id=\"#genetic-background\">Genetic background<\/a><\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\" \/>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-1 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p id=\"sex\" style=\"font-size:18px\"><strong>Sex<\/strong><br>The accumulation of iron in the body over time can cause some haemochromatosis patients to develop complications that impact vital organs and joints. Such complications typically present themselves earlier in males compared to females <a href=\"#refs\" data-type=\"internal\" data-id=\"#refs\">[1]<\/a>, thought to be as a result of iron lost through the menstrual cycle in women. However, symptoms may begin to emerge in females after menopause.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:150px\"><div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"152\" height=\"164\" src=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/image-36.png\" alt=\"\" class=\"wp-image-435\" \/><\/figure><\/div><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-2 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p id=\"age\"><strong>Age<\/strong><br>Because iron accumulation in the body takes a long time to build up and start damaging the organs and joints to a detectable level, signs and symptoms of the disease usually present during middle age (40s and 50s years), with males typically developing symptoms earlier than females.&nbsp; Although, signs and symptoms can still present themselves for the first time in older individuals (&gt;60 years). <a href=\"#refs\" data-type=\"internal\" data-id=\"#refs\">[1]<\/a><\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:150px\"><div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"205\" height=\"152\" src=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/image-38.png\" alt=\"\" class=\"wp-image-439\" \/><\/figure><\/div><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-3 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p id=\"alcohol\"><strong>Alcohol<\/strong><br>Alcohol intake is a well-known risk factor that increases the risk of haemochromatosis, whilst also enhancing the clinical expression of haemochromatosis-related symptoms <a href=\"#refs\" data-type=\"internal\" data-id=\"#refs\">[2]<\/a>. Alcohol consumption has been shown to increase the amount of iron in the body, especially regular excessive alcohol consumption. Being a carrier of a high-risk haemochromatosis genotype, such as two copies of the C282Y variant, plus the consumption of alcohol, can significantly increase the risk of haemochromatosis-related complications, such as liver disease and liver cancer.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:150px\"><div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"145\" height=\"160\" src=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/image-39.png\" alt=\"\" class=\"wp-image-441\" \/><\/figure><\/div><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-4 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p id=\"diet\"><strong>Diet<\/strong><br>Excessive accumulation of iron in the body is the main cause of complications in haemochromatosis. However, it is unclear if controlling dietary iron intake will affect the severity of haemochromatosis symptoms&nbsp;<a rel=\"noreferrer noopener\" href=\"#refs\" target=\"_blank\">[3]<\/a>. Nonetheless, it is important to avoid any iron-based supplements. Please discuss any changes to your diet with a health professional for personalised advice and guidance.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:150px\"><div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"292\" height=\"300\" src=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/image-41.png\" alt=\"\" class=\"wp-image-445\" style=\"width:128px;height:131px\" \/><\/figure><\/div><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-5 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p id=\"obesity\"><strong>Obesity<\/strong><br>The accumulation of excessive fat in the liver, otherwise known as non-alcoholic fatty liver disease (NAFLD), can contribute to raised iron measures in individuals with hemochromatosis. The combination of excess fat in the liver among haemochromatosis patients may exacerbate damage to the liver. Our research found that a high waist-to-hip ratio, a marker of central adiposity, is associated with an increased risk of liver complications in both C282Y homozygous males and females <a href=\"https:\/\/doi.org\/10.1097\/HEP.0000000000001056\">[4]<\/a>.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:150px\"><div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"182\" height=\"252\" src=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/image-49.png\" alt=\"\" class=\"wp-image-887\" style=\"width:116px;height:160px\" \/><\/figure><\/div><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-6 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p id=\"other-genetic-variants\"><strong>Other genetic variants<\/strong><br>There are many common genetic variants that each alter iron levels a little, but which together can cause people with the main <em>HFE <\/em>variants to seriously overload iron <a data-type=\"internal\" data-id=\"#refs\" href=\"#refs\">[5]<\/a>. Also, there are many small effect variants for liver disease, arthritis and diabetes, which can add to a persons risk of getting these diseases with or without <em>HFE <\/em>variants.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-vertically-aligned-center is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:150px\"><div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"181\" height=\"338\" src=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/image-42.png\" alt=\"\" class=\"wp-image-447\" style=\"width:83px;height:156px\" srcset=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/image-42.png 181w, https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/image-42-161x300.png 161w\" sizes=\"(max-width: 181px) 100vw, 181px\" \/><\/figure><\/div><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p id=\"genetic-background\"><strong>Genetic background<\/strong><br>The <em>HFE <\/em>genetic variants are most common in individuals of European genetic ancestry <a data-type=\"internal\" data-id=\"#refs\" href=\"#refs\">[6]<\/a>, especially Northern Europe (indeed, the disease is sometimes known as the &#8220;Celtic curse&#8221;). The figure below shows the C282Y allele frequency (% occurrence) varying over Europe. We therefore restricted our analysis to participants of European genetic ancestry, thus our results do not necessarily reflect risk of haemochromatosis based on HFE genotype for other genetic background.<\/p>\n<\/div>\n<\/div>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"870\" src=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/c282y_frequency_EASL2022-1024x870.jpg\" alt=\"\" class=\"wp-image-151\" srcset=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/c282y_frequency_EASL2022-1024x870.jpg 1024w, https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/c282y_frequency_EASL2022-300x255.jpg 300w, https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/c282y_frequency_EASL2022-768x653.jpg 768w, https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/c282y_frequency_EASL2022-1536x1306.jpg 1536w, https:\/\/sites.exeter.ac.uk\/ironoverload\/wp-content\/uploads\/sites\/193\/2023\/05\/c282y_frequency_EASL2022-2048x1741.jpg 2048w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption class=\"wp-element-caption\">Figure from the <a href=\"https:\/\/doi.org\/10.1016\/j.jhep.2022.03.033\" data-type=\"URL\" data-id=\"https:\/\/doi.org\/10.1016\/j.jhep.2022.03.033\">European Association for the Study of the Liver clinical practice guidelines on haemochromatosis, published 2022 in the Journal of Hepatology<\/a><\/figcaption><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\" \/>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"refs\">References<\/h2>\n\n\n\n<ol>\n<li>Adams PC, Jeffrey G, Ryan J. (2023) &#8220;Haemochromatosis.&#8221; <em>The Lancet<\/em>. doi: <a href=\"http:\/\/doi.org\/10.1016\/s0140-6736(23)00287-8\" data-type=\"URL\" data-id=\"http:\/\/doi.org\/10.1016\/s0140-6736(23)00287-8\">10.1016\/s0140-6736(23)00287-8<\/a><br><\/li>\n\n\n\n<li>Ferrao K, Ali N, Mehta KJ. (2022) &#8220;Iron and iron-related proteins in alcohol consumers: Cellular and clinical aspects.&#8221; <em>Journal of Molecular Medicine<\/em>. doi: <a rel=\"noreferrer noopener\" href=\"https:\/\/doi.org\/10.1007\/s00109-022-02254-8\" data-type=\"URL\" data-id=\"https:\/\/doi.org\/10.1007\/s00109-022-02254-8\" target=\"_blank\">10.1007\/s00109-022-02254-8<\/a><br><\/li>\n\n\n\n<li>Moustarah F, Daley SF. (2023) &#8220;Dietary Iron.&#8221; <em>StatPearls Publishing<\/em>. Available from: <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK540969\/\">https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK540969\/<\/a><\/li>\n\n\n\n<li>Lucas, M. R., Pilling, L. C., Atkins, J. L., &amp; Melzer, D. (2024). Incidence of liver complications with hemochromatosis-associated HFE p.C282Y homozygosity: The role of central adiposity. <em>Hepatology<\/em>. <a href=\"https:\/\/doi.org\/10.1097\/HEP.0000000000001056\">https:\/\/doi.org\/10.1097\/HEP.0000000000001056<\/a><br><\/li>\n\n\n\n<li>Pilling LC, <em>et al.<\/em> (2022) &#8220;Genetic modifiers of penetrance to liver endpoints in HFE hemochromatosis: Associations in a large community cohort.&#8221; <em>Hepatology<\/em>. doi: <a href=\"https:\/\/doi.org\/10.1002\/hep.32575\" data-type=\"URL\" data-id=\"https:\/\/doi.org\/10.1002\/hep.32575\">10.1002\/hep.32575<\/a><br><\/li>\n\n\n\n<li>European Association for the Study of the Liver (2022) &#8220;EASL Clinical Practice Guidelines on haemochromatosis&#8221; <em>Journal of Hepatology<\/em>. doi: <a href=\"https:\/\/doi.org\/10.1016\/j.jhep.2022.03.033\" data-type=\"URL\" data-id=\"https:\/\/doi.org\/10.1016\/j.jhep.2022.03.033\">10.1016\/j.jhep.2022.03.033<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>SexThe accumulation of iron in the body over time can cause some haemochromatosis patients to develop complications that impact vital organs and joints. Such complications typically present themselves earlier in males compared to females [1], thought to be as a result of iron lost through the menstrual cycle in women. However, symptoms may begin to [&hellip;]<\/p>\n","protected":false},"author":293,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"categories":[],"tags":[],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.0 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Other factors modifying risk - Haemochromatosis: genetic iron overload disease<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/sites.exeter.ac.uk\/ironoverload\/other-risk-factors\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Other factors modifying risk - Haemochromatosis: genetic iron overload disease\" \/>\n<meta property=\"og:description\" content=\"SexThe accumulation of iron in the body over time can cause some haemochromatosis patients to develop complications that impact vital organs and joints. Such complications typically present themselves earlier in males compared to females [1], thought to be as a result of iron lost through the menstrual cycle in women. 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