Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration

Despriet, Dominiek D. G.; Klaver, CC W; Witteman, J.C.M.; Bergen, A. A. B.; Kardys, Isabella; Maat, M.P.M. de; Boekhoorn, Sharmila S.; Vingerling, Johannes R.; Hofman, Amy; Oostra, Ben A.; Uitterlinden, André G.; Stijnen, Theo; Duijn, C.M. van; Jong, P.T.V.M. de

doi:10.1016/j.ajo.2006.08.013

Cited by 41 publications

(58 citation statements)

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“…2005). Individuals homozygous for the CFH Y402H polymorphism have a 48% risk of developing late AMD by age 95 years, while this risk does not exceed 22% for noncarriers, and homozygous CFH Y402H carriers have a higher risk of bilateral than of unilateral late AMD (Despriet et al. 2006).…”

Section: Introductionmentioning

confidence: 99%

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Complement factor H Y402H gene polymorphism and response to intravitreal bevacizumab in exudative age‐related macular degeneration

Nischler

Oberkofler

Ortner

et al. 2011

Acta Ophthalmologica

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. Purpose: To determine whether different complement factor H (CFH) genotypes play a role in treatment of age‐related macular degeneration (AMD) with intravitreal bevacizumab. Methods: In this prospective study, we included 197 patients with exudative AMD and treated with 1.25 mg intravitreal bevacizumab at 6‐week intervals until choroidal neovascularization (CNV) was no longer active. In all patients, ophthalmological examinations, visual acuity, optical coherence tomography (OCT), fundus photography and fluorescein angiography were performed. Single nucleotide polymorphism (SNP) genotyping was performed using restriction fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) products. Results: Age, gender and baseline mean visual acuity were similar among the three CFH genotypes. There was no significant difference in underlying lesion type of CNV, lesion size, number of injections or macula thickness. When examining the effect of genotype on post‐treatment visual acuities, we observed a significant worse outcome for distance and reading visual acuity in the CFH 402HH genotype group. The number of patients who lost 3 or more lines in distance and reading visual acuity testing was significantly higher in the CFH 402HH (41%, 46%) genotype group than in patients with the CFH 402YY (28%, 26%) and CFH 402YH (26%, 24%) genotype. Conclusions: In addition to the higher risk for exudative AMD in patients with the CFH 402HH genotype that was found in previous studies, our results show that the CFH 402HH genotype also correlates with lower visual acuity outcome after treatment with bevacizumab, suggesting that pharmacogenetics of CFH plays a role in response to treatment of wet AMD.

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Section: Introductionmentioning

confidence: 99%

“…2004, 2005). Therefore, changes in this region of the protein may result in a malfunctioning CFH that is not able to inhibit this complement cascade properly (Despriet et al. 2006).…”

Section: Introductionmentioning

confidence: 99%

Complement factor H Y402H gene polymorphism and response to intravitreal bevacizumab in exudative age‐related macular degeneration

Nischler

Oberkofler

Ortner

et al. 2011

Acta Ophthalmologica

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“…[32][33][34][35] Complement factor H gene is the main soluble inhibitor of the alternative pathway, which prevents the progression of the cascade by binding and inactivating complement component C3b. 36 The CFH gene has frequent polymorphic variants with the Y402H variant consistently being associated with an increased risk of AMD. [26][27][28][29] People with this variant are unable to sufficiently inhibit the alternative complement cascade which results in chronic damage to the RPE/ Bruch' s membrane interface.…”

Section: Introductionmentioning

confidence: 99%

Chlamydia pneumoniae and age‐related macular degeneration: a role in pathogenesis or merely a chance association?

Guymer

Robman

2007

Clinical Exper Ophthalmology

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The role of inflammation in the aetiology of age-related macular degeneration (AMD) has become very topical as the discovery that genetic variation in complement pathway genes influences the risk of developing AMD. Complement factor H gene, an inhibitor of the alternative complement activation pathway along with other complement pathway genes factor F (BF) and C2 show significant contribution to the risk of AMD. The alternative complement pathway is activated by a trigger, which is often microbial in nature. One current model of AMD aetiology implicates aberrant regulation of the alternative pathway of complement, in combination with some unknown infectious agents. Chlamydia pneumoniae could be one such potential trigger of the alternative complement pathway and several investigations have linked C. pneumoniae to AMD. However, there are only a few studies to date and numbers in most studies are small. Also there are many difficulties in verifying laboratory techniques for the detection of C. pneumoniae chronic infection. As such we need to be cautious not to over interpret the current results. However, the findings certainly give impetus for further work on C. pneumoniae and AMD. This paper provides an overview of work in this area.

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“…These genes account for a substantial proportion of the genetic predisposition associated with the disease. 10,12,19,21 Of the genes thus far identified, a majority play roles in the immune/inflammatory system. These include the complement factor H gene (CFH) on the long arm of chromosome 1, 12-15 the complement factor B (CFB) and the complement component 2 (C2) genes localized within the major histocompatibility complex class III region on chromosome 6, 10 the complement C3 gene on chromosome 19p 11 and the CFH paralogous genes (CFHR3, CFHR1, CFHR4, CFHR2 and CFHR5) that are arranged in tandem on chromosome 1 and present as partial duplications of the CFH gene associated with a protective effect for AMD.…”

Section: Genetic Associationsmentioning

confidence: 99%

“…It is estimated that greater than 50% of AMD individuals present with high-risk alleles at the CFH, LOC387715 and C2/BF loci. 10,12,19,21 In particular, analysis of five SNPs in these genes indicated that 10% of the study population had a 40-fold increased risk of AMD, whereas individuals who were homozygous for all risk variants had a 285-fold greater risk compared with the lowest risk group. 53 However, although this comparison is valid it also argues as to whether these findings improve prediction of endstage AMD in individuals at risk.…”

Section: Predictive Power Of Genetic Testing Of Multiple Snpsmentioning

confidence: 99%

New era for personalized medicine: the diagnosis and management of age‐related macular degeneration

Baird

Hageman

Guymer

2009

Clinical Exper Ophthalmology

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It can be argued that age-related macular degeneration is one of the best characterized complex trait diseases. Extensive information related to genetic and environmental risk factors exists, and a number of different biological pathways are strongly implicated in its aetiology. Along with recent improvements in high throughput and relatively inexpensive genetic technologies, we are now in a position to consider developing a presymptomatic, personalized approach towards the assessment, management and treatment of this disease. We explore the applicability and challenges of this approach if it is to become commonplace for guiding treatment decisions for individuals with pre-existing disease or for those at high risk of developing it.

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Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration

Cited by 41 publications

References 0 publications

Complement factor H Y402H gene polymorphism and response to intravitreal bevacizumab in exudative age‐related macular degeneration

Complement factor H Y402H gene polymorphism and response to intravitreal bevacizumab in exudative age‐related macular degeneration

Chlamydia pneumoniae and age‐related macular degeneration: a role in pathogenesis or merely a chance association?

New era for personalized medicine: the diagnosis and management of age‐related macular degeneration

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