Complement factor H Y402H gene polymorphism, C-reactive protein, and risk of incident myocardial infarction, ischaemic stroke, and venous thromboembolism: A nested case–control study

Zee, Robert Y.L.; Diehl, Kirsti A.; Ridker, Paul M.

doi:10.1016/j.atherosclerosis.2005.09.009

Cited by 45 publications

(27 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondly, it may be anticipated that the gene variants linked to AMD also contribute to other prevalent age-related diseases where chronic, local inflammatory processes are involved. For example, a significant statistical relationship between the CFH Tyr402His 'risk' variant and the incidence of myocardial infarction has recently been reported (242,244). Based upon this new genetic information, it will now be possible to devise genetic screening tests that will identify those individuals who are most at risk of developing AMD later in life.…”

Section: Resultsmentioning

confidence: 99%

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

et al. 2006

View full text Add to dashboard Cite

Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden.Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage 'wet' form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common 'dry' AMD, except for the use of antioxidants that delay progression in 20%-25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene-which encodes the major inhibitor of the complement alternative pathway-is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan.

show abstract

Section: Resultsmentioning

confidence: 99%

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The substitution of a positively charged histidine for a non-charged hydrophobic tyrosine in position 402 may alter the binding properties and consequently have functional implications. Recently, an association of the Tyr402His polymorphism with risk of vascular events could not be demonstrated in a nested case-control study within the Physicians' Health study (26). The authors report that they had the ability to detect, with 80% power, at an alpha of 0.05, a risk ratio of Ͼ1.35 for the His variant for vascular events (myocardial infarction, ischemic stroke, deep venous thrombosis/ pulmonary embolism, n ϭ 685).…”

Section: Discussionmentioning

confidence: 99%

A Common Polymorphism in the Complement Factor H Gene Is Associated With Increased Risk of Myocardial Infarction

Kardys

Klaver

Despriet

et al. 2006

Journal of the American College of Cardiology

View full text Add to dashboard Cite

show abstract

“…Factor H is a complement regulator, and polymorphisms, especially Y402H, in the Factor H-gene is extensively studied and associated with age-related macular degeneration (Gehrs et al, 2010). There are conflicting results about the Y402H polymorphisms and cardiovascular disease including myocardial infarction, but most studies find no association, so the importance of factor H variants in cardiovascular disease at present is unclear (Zee et al, 2006;Kardys et al, 2006;Nicaud et al, 2007;Stark et al, 2007;Sofat et al, 2010). Thus, some variants in genes encoding proteins of the complement system including MBL and C3 are associated with risk for coronary heart disease, while in others like factor H appear to be more uncertain.…”

Section: Genetic Studies On the Complement System And Risk Of Coronarmentioning

confidence: 99%

A vital role for complement in heart disease

Lappegård

Garred

Jonasson

et al. 2014

Molecular Immunology

View full text Add to dashboard Cite

Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention.

show abstract

Complement factor H Y402H gene polymorphism, C-reactive protein, and risk of incident myocardial infarction, ischaemic stroke, and venous thromboembolism: A nested case–control study

Cited by 45 publications

References 10 publications

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

A Common Polymorphism in the Complement Factor H Gene Is Associated With Increased Risk of Myocardial Infarction

A vital role for complement in heart disease

Contact Info

Product

Resources

About