The Y402H variant of complement factor H is associated with age-related macular degeneration but not with diabetic retinal disease in the Go-DARTS study

A. S. F. Doney, G. P. Leese, J. Olson, A. D. Morris, C. N. A. Palmer

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    The Y402H variant of complement factor H (CFH) is associated with risk of age-related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening.

    Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models.

    The retrospective study demonstrated that the HH genotype was associated with an age-adjusted odds ratio of 7.4 for ARMD (P = 2.9 x 10(-11)). In a longitudinal study in the disease-free cohort, the age-adjusted hazard ratio was 2.8 (P = 2.4 x 10(-7)). The life-time hazard ratio was 3.4 (P = 2.1 x 10(-16)). We found no association of Y402H with development of referable diabetic retinal disease.

    The ARMD-associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions.

    Original languageEnglish
    Pages (from-to)460-465
    Number of pages6
    JournalDiabetic Medicine
    Volume26
    Issue number5
    DOIs
    Publication statusPublished - May 2009

    Keywords

    • age-related macular degeneration
    • complement factor H
    • diabetic retinopathy
    • Type 2 diabetes
    • C-REACTIVE PROTEIN
    • ADVANCED GLYCATION
    • DRUSEN FORMATION
    • RETINOPATHY
    • RISK
    • PATHOGENESIS
    • CFH
    • POLYMORPHISM
    • ACTIVATION
    • INHIBITORS

    Cite this

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    title = "The Y402H variant of complement factor H is associated with age-related macular degeneration but not with diabetic retinal disease in the Go-DARTS study",
    abstract = "The Y402H variant of complement factor H (CFH) is associated with risk of age-related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening.Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models.The retrospective study demonstrated that the HH genotype was associated with an age-adjusted odds ratio of 7.4 for ARMD (P = 2.9 x 10(-11)). In a longitudinal study in the disease-free cohort, the age-adjusted hazard ratio was 2.8 (P = 2.4 x 10(-7)). The life-time hazard ratio was 3.4 (P = 2.1 x 10(-16)). We found no association of Y402H with development of referable diabetic retinal disease.The ARMD-associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions.",
    keywords = "age-related macular degeneration, complement factor H, diabetic retinopathy, Type 2 diabetes, C-REACTIVE PROTEIN, ADVANCED GLYCATION, DRUSEN FORMATION, RETINOPATHY, RISK, PATHOGENESIS, CFH, POLYMORPHISM, ACTIVATION, INHIBITORS",
    author = "Doney, {A. S. F.} and Leese, {G. P.} and J. Olson and Morris, {A. D.} and Palmer, {C. N. A.}",
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    T1 - The Y402H variant of complement factor H is associated with age-related macular degeneration but not with diabetic retinal disease in the Go-DARTS study

    AU - Doney, A. S. F.

    AU - Leese, G. P.

    AU - Olson, J.

    AU - Morris, A. D.

    AU - Palmer, C. N. A.

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    N2 - The Y402H variant of complement factor H (CFH) is associated with risk of age-related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening.Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models.The retrospective study demonstrated that the HH genotype was associated with an age-adjusted odds ratio of 7.4 for ARMD (P = 2.9 x 10(-11)). In a longitudinal study in the disease-free cohort, the age-adjusted hazard ratio was 2.8 (P = 2.4 x 10(-7)). The life-time hazard ratio was 3.4 (P = 2.1 x 10(-16)). We found no association of Y402H with development of referable diabetic retinal disease.The ARMD-associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions.

    AB - The Y402H variant of complement factor H (CFH) is associated with risk of age-related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening.Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models.The retrospective study demonstrated that the HH genotype was associated with an age-adjusted odds ratio of 7.4 for ARMD (P = 2.9 x 10(-11)). In a longitudinal study in the disease-free cohort, the age-adjusted hazard ratio was 2.8 (P = 2.4 x 10(-7)). The life-time hazard ratio was 3.4 (P = 2.1 x 10(-16)). We found no association of Y402H with development of referable diabetic retinal disease.The ARMD-associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions.

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    KW - ADVANCED GLYCATION

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    KW - RISK

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    KW - INHIBITORS

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