Association of the complement factor H Y402H polymorphism with cardiovascular disease is dependent upon hypertension status: The ARIC study.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Volcik
Kelly A
KA
Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA. Volcik@uth.tmc.edu
Ballantyne
Christie M
CM
Braun
Michael C
MC
Coresh
Josef
J
Mosley
Thomas H
TH
Boerwinkle
Eric
E
D001741:Black or African American / Q000235:genetics; D002545:Brain Ischemia / Q000209:etiology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D002340:Carotid Artery Diseases / Q000209:etiology / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000235:genetics; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
C493495:CFH protein, human; D017242:Complement Factor H