Analysis ofCFH,TLR4, andAPOEPolymorphism in India Suggests the Tyr402His Variant ofCFHto be a Global Marker for Age-Related Macular Degeneration

Kaur, Inderjeet; Hussain, Avid; Hussain, Nazimul; Das, Taraprasad; Pathangay, Avinash; Mathai, Annie; Hussain, Anjli; Nutheti, Rishita; Nirmalan, Praveen K; Chakrabarti, Subhabrata

doi:10.1167/iovs.05-1430

Cited by 69 publications

(57 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results have been replicated in other studies [112,113,114,115,116,117,118,119,120,121,122] and confirmed by a meta-analysis [123]. However, likely because of the weak allele effects of Apo-ε, and because of the low allele frequencies of both the ε2 and ε4 alleles, some studies could not demonstrate any association between this gene and AMD [124,125,126,127,128,129].…”

Section: Genetic Factors Associated With Amdsupporting

confidence: 78%

Genetic Factors Associated with Age-Related Macular Degeneration

et al. 2011

View full text Add to dashboard Cite

show abstract

Section: Genetic Factors Associated With Amdsupporting

confidence: 78%

Genetic Factors Associated with Age-Related Macular Degeneration

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Both CFH and FHL-1 are present in vitreous fluid of eye and expressed by RPE cells (Skerka et al, 2007). A tyrosine to histidine mutation at codon 402 (Y402H) within CFH is strongly associated with AMD pathology (Rivera et al, 2005;Klein et al, 2005;Edwards et al, 2005;Haines et al, 2005;Hageman et al, 2005) and has been suggested to be a global marker for AMD (Kaur et al, 2006). The tyrosine residue at position (CFH YY402 ) is considered as protective variant whereas the histidine residue at this position (CFH YH402 and CFH HH402 ) a risk variant for AMD.…”

Section: Complement and Age-related Macular Degenerationmentioning

confidence: 99%

The role of complement system in ocular diseases including uveitis and macular degeneration

Jha

Bora

2007

Molecular Immunology

111

View full text Add to dashboard Cite

In the normal eye, the complement system is continuously activated at low levels and both membranebound and soluble intraocular complement regulatory proteins tightly regulate this spontaneous complement activation. This allows protection against pathogens without causing any damage to self-tissue and vision loss. The complement system and complement regulatory proteins control the intraocular inflammation in autoimmune uveitis and play an important role in the development of corneal inflammation, age-related macular degeneration and diabetic retinopathy. The evidence derived from both animal models and patient studies support the concept that complement inhibition is a relevant therapeutic target in the treatment of various ocular diseases. Currently, several clinical trials using complement inhibitors are going on. It is possible that, in the near future, complement inhibitors might be used as therapeutic agents in eye clinics.

show abstract

“…Interestingly, Zareparsi et al reported an association of Toll-like receptor 4 and AMD 35 , in contradistinction to atherosclerosis, where this seems to induce protection. However, in an evaluation of a cohort of AMD patients in India, no association was found with Toll-receptor 4, while one was found with complement factor H. 36 …”

Section: Other Genesmentioning

confidence: 97%

Age-related Macular Degeneration and the Immune Response: Implications for Therapy

Nussenblatt

Ferris

2007

American Journal of Ophthalmology

116

101

View full text Add to dashboard Cite

Purpose-Review of the available information concerning the immune mediation of age related macular degeneration (AMD); speculate on proposed mechanisms and immuno-therapy. Design-Interpretative essay Methods-Literature review and interpretationResults-An ever growing body of evidence is gathering concerning the role of the immune system in AMD. Evidence to date suggests that the underlying mechanism leading to AMD is the decline of the ocular downregulatory immune environment (DIE). The subsequent activation of the immune system would lead to T cell sensitization. When combined with local anti-angiogenic therapy, several existing immuno-therapies could be used to downregulate the immune response and potentially leading to a more efficient inhibition of choroidal neovascularization.Age related macular degeneration is currently the leading cause of blindness in the United States and its prevalence will continue to increase in the coming decades unless new prevention strategies can be developed. 1 Currently over 1.75 million US citizens are affected with advanced AMD, and this number is likely to increase to nearly 3 million by the year 2020 due to the increased number of aging US citizens. Population studies have helped to determine risk factors for this disorder. 2 Some of the non-modifiable factors include age, family history/ genetic factors, light colored iris, and hyperopia. Some of the modifiable risk factors include cigarette smoking, diet, high blood pressure, and possibly elevated serum cholesterol or increased light exposure. The association of these risk factors with the risk of advanced AMD can provide clues as to what causes the disease to develop and how one might prevent the disease. For example, cigarette smoking may increase the risk of AMD through enhancement of the immune cascade. 3 The progression of AMD may be similar to the mechanisms of progression for atherosclerosis, which is now considered to be an inflammatory disease. 4 This provides a new approach to understanding the development and potentially the treatment of this disease. The atheromatous lesion is believed to be inflammatory and it is conjectured that the autoantigen LDL is a driving factor. 5,6 The immune response and cytokine status appear to have profound effects on the disease, with IL-10 loss associated with an increase in the numbers of atheromatous lesions, while deficiencies in IFN-gamma and IL-18 are associated

show abstract

Analysis ofCFH,TLR4, andAPOEPolymorphism in India Suggests the Tyr402His Variant ofCFHto be a Global Marker for Age-Related Macular Degeneration

Abstract: The CFH polymorphism Tyr402His appears indicative of AMD pathogenesis. Diabetes, age, and gender in the presence of the homozygous "CC" genotype in CFH carry an increased risk of AMD. Hence this polymorphism could be used as a potential marker for predictive testing across continents.

Cited by 69 publications

References 41 publications

Genetic Factors Associated with Age-Related Macular Degeneration

Genetic Factors Associated with Age-Related Macular Degeneration

The role of complement system in ocular diseases including uveitis and macular degeneration

Age-related Macular Degeneration and the Immune Response: Implications for Therapy

Contact Info

Product

Resources

About