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Association of the complement factor H Y402H polymorphism with cardiovascular disease is dependent upon hypertension

Kelly A Volcik1, Christie M Ballantyne, Michael C Braun

  • 1Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA. Volcik@uth.tmc.edu

American Journal of Hypertension
|February 23, 2008
PubMed

Insights

The Complement factor H (CFH) 402H allele increases risk for coronary heart disease (CHD) and ischemic stroke in whites. Hypertension amplifies this association, particularly for CHD and carotid artery thickness.

Area of Science:

  • Genetics and Cardiovascular Disease
  • Complement System Biology
  • Epidemiology of Atherosclerosis

Background:

  • Complement factor H (CFH) regulates the alternative complement pathway and is implicated in atherogenesis.
  • The Y402H polymorphism in CFH is a key area of investigation for cardiovascular risk.
  • Understanding CFH's role is crucial for developing targeted interventions against atherosclerosis.

Purpose of the Study:

  • To investigate the association of the CFH Y402H polymorphism with incident coronary heart disease (CHD).
  • To evaluate the link between the CFH Y402H polymorphism and incident ischemic stroke.
  • To determine the relationship between the CFH Y402H polymorphism and carotid artery intima-media thickness (IMT).

Main Methods:

  • The Atherosclerosis Risk in Communities (ARIC) cohort was utilized for this study.
  • Incident CHD and ischemic stroke were ascertained through comprehensive surveillance methods.
  • Carotid intima-media thickness (cIMT) was measured using high-resolution B-mode ultrasound.

Main Results:

  • The 402HH genotype significantly predicted incident ischemic stroke in white individuals (HRR 1.47).
  • Hypertension interacted significantly with the CFH genotype for CHD and cIMT in whites, and for cIMT in African Americans.
  • The 402H allele was associated with increased CHD risk in hypertensive whites and higher cIMT in whites, with or without hypertension.

Conclusions:

  • The CFH 402H allele is linked to a higher risk of incident CHD and ischemic stroke in white populations.
  • The impact of the CFH 402H allele on cardiovascular risk is modulated by hypertension status.
  • These findings highlight the role of the complement system in atherogenesis and stroke risk.
Abstract

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