Association of the Complement Factor H Y402H Polymorphism With Cardiovascular Disease Is Dependent Upon Hypertension Status: The ARIC Study

Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA.
American Journal of Hypertension (Impact Factor: 2.85). 06/2008; 21(5):533-8. DOI: 10.1038/ajh.2007.81
Source: PubMed


Complement factor H (CFH) is a plasma protein that is essential in the regulation of the alternative complement pathway and has been implicated as taking part in complement inhibition in atherogenesis. We evaluated the association of the Y402H polymorphism with incident coronary heart disease (CHD), incident ischemic stroke, and carotid artery wall thickness (intima-media thickness (IMT)) in the Atherosclerosis Risk in Communities (ARIC) cohort.
Incident ischemic stroke and CHD were identified through annual telephone calls and hospital and death certificate surveillance. Carotid IMT was measured by means of high-resolution B-mode ultrasound. Four hundred eighty-three validated ischemic stroke and 1,544 CHD events were identified. Because of allele frequency differences between whites and African Americans, analyses were performed separately according to the racial group.
The 402HH homozygous genotype was a significant predictor of incident ischemic stroke in whites (hazard rate ratio (HRR) 1.47, 95% confidence interval (CI) 1.05-2.05). Significant interaction effects between genotype and hypertension were observed for CHD in whites and for cIMT in whites and African Americans. In further analyses of incident CHD, genotypes carrying the 402H allele were a significant predictor of incident CHD in whites who had hypertension (402YH: HRR 1.19, 95% CI 1.01-1.40; 402HH: HRR 1.28, 95% CI 1.04-1.57). The 402H allele was also associated with higher cIMT measures for whites in the overall cohort, and for whites with hypertension.
The CFH 402H allele was associated with an increased risk for incident CHD and ischemic stroke in whites, with the strength and significance of the association dependent upon hypertension status.

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    • "Boiocchi et al. [54] demonstrated that complement receptor I (CR1) gene polymorphisms may be involved in the predisposition to the development of the disease. More interestingly, the same CFH Y402H polymorphism that is associated with the risk of AMD, is found to be associated with increased incidence of atherosclerosis in hypertensive white individuals [55]. "
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    • "Some studies have also shown an association between the rs1061170 (Y402H) polymorphism and the incidence of myocardial infarction and coronary artery disease [26], [27]. Indeed several clinical trials using complement inhibitors in both AMD and atherosclerosis are currently under way [24]. "
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    • "According to the initial report of Kardys et al. (2006) a positive association between Y402H and the incidence of myocardial infarction in the Rotterdam Study was observed. Following this report, data from the large population-based study of Volcik et al. (2008) showed a direct link between the Y402H polymorphism and the incidence of coronary artery disease, particularly in white hypertensive individuals . In addition, a strong positive correlation between the unfavourable CFH variant and higher carotid artery wall thickness in white patients was observed. "
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