The cardiomyopathy of idiopathic or acquired haemochromatosis suggests that the heart may be especially sensitive to toxic effects of excess iron (Sullivan 1990). The features of inherited iron overload include cardiac problems (arrhythmias and heart failure), and/or cirrhosis of the liver, diabetes, arthritis and skin pigmentation. Since haemochromatosis can be easily treated by phlebotomy once diagnosed, this condition is considered a preventable form of heart disease amongst other equally important health risks.


Not only homozygosity for the HFE C282Y mutation, but also the heterozygous state is associated with increased serum iron parameters (Rossi et al. 2001). Individuals with serum transferrin saturation levels above 55% carry an increased all-cause mortality risk especially when combined with high red meat intake (Mainous et al. 2004a,b). Coronary heart disease rates rise sharply from age 20 onwards in males, who begin accumulating excess iron from late adolescence. Healthy women, on the other hand, do not accumulate excess iron in their tissues until after the menopause, when they rapidly develop the same risk of CVD as men of the same age. Detection of an association between heterozygosity for mutation C282Y and increased risk of acute myocardial infarction in men (Tuomainen et al. 1999), as well as with cardiovascular death in postmenopausal women (Roest et al. 1999), support the iron-heart link. The risk of cardiovascular death in postmenopausal women with at least one copy of the C282Y mutation appeared to be stronger in women who were hypertensive or current smokers, with a nearly 20-fold increased risk when both risk factors were present, compared with nonsmokers, nonhypertensives, and noncarriers. This finding again emphasised the importance of multiple risk factor assessment when low-expression mutations are analysed.


The potential combined effects of elevated body iron stores and hypercholesterolaemia is of particular concern, as two independent studies demonstrated worse clinical outcomes under such circumstances (Salonen et al. 1992; Wells et al. 2004). Persons with both elevated transferrin saturation and elevated LDL showed a significantly greater risk for CVD mortality than persons when both parameters normal or elevated LDL without elevated transferrin saturation.


Recent studies performed in the South African population demonstrated the significance of LDL particle size as a risk factor for CVD in patients with non-alcoholic liver disease (NAFLD), while the presence of HFE mutations may be associated with disease severity in some families (FC Kruger 2008, PhD study). Due to the findings relating to dyslipidaemia, obesity and insulin resistance in the South African study cohort, a diagnosis of NAFLD or metabolic syndrome is regarded an important indication for referral of chronic disease risk management, including the assessment of multiple genetic risk factors for CVD performed in conjunction with a medical and lifestyle/nutrition assessment (Kotze and Badenhorst 2005).


Kotze MJ, Badenhorst H. Chronic disease risk management: Combining genetic testing with medical and nutrition therapy. SA Fam Pract 2005; 47 (4): 40-42.

Mainous AG III, Gill JM, Pearson WS, Carek PJ. Elevated serum transferrin saturation and mortality. Ann Fam Med 2004a; 2: 133-138.

Mainous AG III, Wells BJ, Carek PJ, et al. The mortality risk of elevated serum transferrin saturation and consumption of dietary iron. Ann Fam Med 2004b, 2: 139-144.

Milani MY, Kotze MJ. Molecular diagnosis of hereditary haemochromatosis: identify an affected person and save a family. S Afr Med J 1999; 89: 263-264.

Roest M, van der Schouw YT, de Valk B, et al. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Circulation 1999; 100: 1268-1273.


Rossi E, Bulsara MK, Olynyk JK, et al. Effect of hemochromatosis genotype and lifestyle factors on iron and red cell indices in a community population. Clin Chem 2001; 47: 202-208.

Salonen JT, Nyyssonen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men. Circulation 1992; 86: 803-811.

S ullivan JL. Heterozygous haemochromatosis as a risk factor for premature myocardial infarction. Medical Hypotheses 1990; 31: 1-5.

Tuomainen T-P, Kontula K, Nyyssonen K, et al. Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation. A prospective cohort study in men in Eastern Finland. Circulation 1999; 100: 1274-1279.


Wells BJ, Mainous AG III, King DE, et al. The combined effect of transferrin saturation and low density lipoprotein on mortality. Fam Med 2004; 36: 324-329.


Research Initiative:

This genetic testing service is combined with an ethically approved research project to enable us to monitor the success of a wellness initiative in collaboration with the referring clinician. Patients will be assisted to sign the research informed consent form that may be be provided together with a sample collection kit. EDTA blood (purple top tube) can also be provided for DNA testing when the informed consent form is downloaded from this website.

Patients are encouraged to contact Professor Maritha Kotze (maritha@sun.ac.za / info@gknowmix.com;  tel. 27 21 9389324 / 0828799108) with any questions they may have about the research or test-related payment.

A quote for the amount due will be emailed to you once the service request has been entered online. Please provide the contact details of the consulting healthcare practitioner for participation.

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