Clinical study
Prevalence of coronary heart disease associated with HFE mutations in adults attending a health appraisal center

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Abstract

Purpose

Mutations of the HFE gene that cause hereditary hemochromatosis may be associated with an increased risk of cardiovascular disease. We examined the relation between two HFE mutations (C282Y and H63D), indicators of iron homeostasis, and the prevalence of coronary heart disease in a large population of white adults.

Subjects and methods

We conducted a cross-sectional study of 30,916 white adults aged 25 to 98 years who attended a health appraisal center and underwent screening for HFE mutations. Coronary heart disease and cardiovascular risk factors were ascertained by questionnaire and medical records.

Results

Overall, 12% (1798/15,362) of men and 7% (1074/15,554) of women had a history of coronary heart disease. Of 10 HFE genotypes tested (five genotypes by sex), only men with the C282Y/H63D genotype (compound heterozygotes) had a significantly higher prevalence of coronary heart disease compared with men with no HFE mutations (odds ratio = 1.6; 95% confidence interval: 1.1 to 2.4; P = 0.01) after adjusting for cardiovascular risk factors. Elevated serum ferritin levels (>250 ng/mL) were associated with a lower prevalence of coronary heart disease in men (10% [255/2209] vs. 12% [1515/12,461] in controls, P = 0.008), which was not significant after adjusting for use of aspirin and anticoagulants. There were no significant associations between elevated transferrin saturation in either men or women, or between elevated serum ferritin levels or HFE mutations in women, and the prevalence of coronary heart disease.

Conclusion

The results do not support a consistent association between HFE mutations or serum iron indicators and the prevalence of coronary heart disease.

Section snippets

Subjects and methods

The sample consisted of 30,916 white, non-Hispanic, adult patients aged 25 to 98 years who were attending the Health Appraisal Center at Kaiser Permanente, San Diego, California. All subjects gave informed consent to be screened for hemochromatosis by HFE genotyping. During any given 4-year period, approximately 81% of Kaiser enrollees attend the center; all patients attending were offered the opportunity to participate in the study. Those who consented represented 46% of all white,

Results

The sample consisted of 15,362 men (49.7%) and 15,554 women (Table 1). Mean transferrin saturation and ferritin levels varied by HFE genotype, with highest values occurring in C282Y homozygotes (C282Y/C282Y), followed by compound heterozygotes (C282Y/H63D), H63D homozygotes (H63D/H63D), C282Y heterozygotes (C282Y/wt), H63D heterozygotes (H63D/wt), and wild types (wt/wt) in both men and women (Table 1).

The overall prevalence of coronary heart disease was 12% (n = 1798) among men and 7% (n =

Discussion

In this large cross-sectional study of more than 30,000 white adults attending a health appraisal center, we found an increased odds of coronary heart disease among only one of 10 HFE genotype groups compared with sex-specific wild-type controls: male compound heterozygotes (C282Y/H63D) had a 1.6-fold increased odds of coronary heart disease after adjusting for age and other known cardiovascular risk factors. There were no significant associations among pooled carriers of the C282Y or the H63D

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    Supported by grants DK53505-02 and RR00833 from the National Institutes of Health, Bethesda, Maryland, and supplemented with a grant from the Division of Nutrition and Physical Activity, Centers for Disease Control and Prevention, Atlanta, Georgia, and funds from the Stein Endowment Fund, San Diego, California.

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