Correlation of hemochromatosis gene mutations and cardiovascular disease in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) is a major cause of death in hemodialysis (HD) patients. Hemochromatosis (HFE) gene mutations are reported to be associated with CVD. The present study aims to investigate the association of HFE gene polymorphism with CVD in HD patients.

DESIGN AND SETTINGS: Cross-sectional case-control.

METHODS: C282Y/H63D mutations of HFE gene were evaluated in 560 HD patients and 480 healthy controls from 4 HD centers in North China. The results obtained from this evaluation process were correlated with biochemical parameters including iron status (serum iron, ferritin, and transferrin concentration), cardiovascular disease, and inflammation marker CRP, IL-6, TNF-a.

RESULTS: No C282Y mutations were detected in HD patients or healthy controls in this study. The genotype of H63D heterozygous mutation was similar in HD patients with CVD, HD patients without CVD, and controls. H63D homozygous mutation was 7.4% (19/257), 3.1% (9/303), and 1.0% (5/480) for the 3 groups, respectively. Compound heterozygosity was not found in this study. The relative risk for CVD in HD patients with H63D homozygous mutation was 2.59 (95% CI: 1.15-5.84). H63D homozygous mutation had significantly higher serum ferritin concentrations compared with wild-type individuals. Moreover, HD patients had significantly higher levels of inflammatory biomarkers such as CRP, IL-6, and TNF-a. The multivariate logistic regression analysis revealed that H63D mutation instead of ferritin level was an independent risk factor of CVD for HD patients.

CONCLUSIONS: Our study demonstrates for the first time that there was an association between H63D homozygous mutations and CVD in HD patients. Elevated serum CRP, IL-6, and TNF-a levels were also related to CVD in HD patients.