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Haemochromatosis mutations and ferritin in myocardial infarction: a case-control study
Dirk Claeys1, M Walting, F Julmy
1Swiss Heart Center, Thrombosis Research Laboratory, Kinder Klinik G4, University Hospital Bern, CH-3010 Bern, Switzerland. dirk.claeys@dkf2.unibe.ch
Insights
Genetic haemochromatosis was not linked to myocardial infarction in Swiss whites. However, elevated ferritin levels in patients suggest increased iron stores may play a role in heart disease risk.
Area of Science:
- Cardiovascular Disease Research
- Genetics and Human Health
- Nutritional Biochemistry
Background:
- Iron accumulation is implicated in coronary heart disease (CHD) pathogenesis through free radical formation and LDL oxidation.
- Epidemiological data on iron status and CHD risk remain inconsistent.
- Genetic haemochromatosis is an inherited disorder causing excessive iron absorption.
Purpose of the Study:
- To investigate the association between genetic haemochromatosis and myocardial infarction (MI).
- To examine the relationship between plasma ferritin levels and MI risk.
Main Methods:
- A case-control study involved 177 MI survivors and 89 controls.
- Prevalence of three HFE gene mutations (Cys282Tyr, His63Asp, Ser65Cys) was determined using PCR and restriction enzyme digestion.
- Plasma ferritin levels were measured and correlated with MI risk.
Main Results:
- No significant differences in carrier frequencies for HFE mutations were observed between MI patients and controls.
- Mean plasma ferritin levels were higher in MI patients (176 μg/L) than in controls (131 μg/L).
- Unadjusted analysis showed a 2.9-fold increased risk of MI for individuals with ferritin levels ≥300 μg/L, but this association lost significance after adjusting for other cardiovascular risk factors.
Conclusions:
- Genetic haemochromatosis is not directly associated with myocardial infarction in the studied Swiss white population.
- Elevated ferritin levels in MI patients suggest a potential role for increased iron stores in CHD.
- Iron overload was not identified as an independent risk factor for coronary heart disease in this cohort.
Background:
Iron accumulation may contribute to coronary heart disease by catalysing free radical formation and promoting oxidation of low-density lipoprotein cholesterol. Epidemiological studies of iron status and coronary heart disease are conflicting.
Design:
To test whether genetic haemochromatosis is associated with myocardial infarction, we determined the prevalence of three mutations in the HFE gene (Cys282Tyr, His63Asp and Ser65Cys) in a 2 : 1 case-control study including 177 patients who survived an acute myocardial infarction and 89 controls. Genotypes were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. We also studied the relationship between plasma ferritin and myocardial infarction.
Results:
The carrier frequencies of these three mutations were not statistically different among patients and controls (Cys282Tyr: 1.4 vs. 10.1%; His63Asp: 26.5 vs. 31.5%; Ser65Cys: 2.8 vs. 1.1%). Mean ferritin levels were elevated among patients (176 +/- 155 microg L(-1)) compared with controls (131 +/- 106 microg L(-1), P = 0.015). Subjects with plasma ferritin concentrations of 300 microg L(-1) or more had a 2.9-fold (95% CI: 1.2-7.3, P = 0.02) unadjusted risk for a myocardial infarction compared with those with normal levels. In a univariate analysis, ferritin was significantly associated with myocardial infarction. Upon multiple regression analysis adjusting for smoking, hypertension, diabetes, body-mass index and total cholesterol, significance was no longer present.
Conclusions:
No direct association was found between genetic haemochromatosis and myocardial infarction among Swiss whites. Raised ferritin levels among patients suggest a role of increased iron stores in myocardial infarction, but iron overload was not an independent risk factor for Swiss coronary heart disease patients.