Association Between Complement Factor<i>C2/C3/CFB/CFH</i>Polymorphisms and Age-Related Macular Degeneration: A Meta-Analysis

Lü, Fangli; Liu, Shuang; Hao, Qingyun; Liu, Lixia; Zhang, Jing; Chen, Xiaolong; Wang, Hu; Huang, Peng

doi:10.1089/gtmb.2018.0110

Cited by 29 publications

(31 citation statements)

References 78 publications

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“…Eculizumab is an effective terminal pathway blocker; however, for several years its use has been restricted to only two ultra‐rare diseases, PNH and aHUS, and latterly approved for MG treatment. In recent years, pathological roles of complement in more common conditions like MG, age‐related macular degeneration and neurodegeneration have been demonstrated, building a case for the broader use of anti‐complement drugs in the clinic . Cost and convenience are limiting factors in broadening anti‐complement drug use; current cost and dosing schedules for Eculizumab are incompatible with use in the treatment of common, chronic diseases.…”

Section: Discussionmentioning

confidence: 99%

Development and characterization of novel anti‐C5 monoclonal antibodies capable of inhibiting complement in multiple species

2019

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Summary Over the last decade there has been an explosion in complement therapies; one‐third of the drugs in the clinic or in development target C5 protein. Eculizumab, a monoclonal antibody (mAb) that binds C5 and blocks its cleavage by the convertase, is the current reference standard treatment for atypical haemolytic uraemic syndrome (aHUS) and paroxysmal nocturnal haemoglobinuria (PNH) and in clinical trials for many other diseases. Here we describe a panel of novel anti‐C5 mAb, including mAb that, like Eculizumab, are efficient inhibitors of complement but, unlike Eculizumab, inhibit across species, including human, rat, rabbit and guinea pig. Several inhibitory anti‐C5 mAb were identified and characterized for C5 binding and lytic inhibitory capacity in comparison to current therapeutic anti‐C5 mAb; three clones, 4G2, 7D4 and 10B6, were selected and further characterized for ligand specificity and affinity and cross‐species inhibitory activity. The mAb 10B6 was human‐specific whereas mAb 4G2 and 7D4 efficiently inhibited lysis by human, rabbit and rat serum, and weakly inhibited guinea pig complement; 7D4 also weakly inhibited mouse complement in vitro The rat C5‐cross‐reactive mAb 4G2, when administered intraperitoneally in a rat model of myasthenia gravis, effectively blocked the disease and protected muscle endplates from destruction. To our knowledge this is the first report of an anti‐C5 function blocking mAb that permits preclinical studies in rats.

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Section: Discussionmentioning

confidence: 99%

Development and characterization of novel anti‐C5 monoclonal antibodies capable of inhibiting complement in multiple species

2019

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“…Wang et al performed a systematic analysis and suggested rs641153 in the CFB gene was a protective factor in advanced AMD both in Caucasians and Asians [17]. Rs547154 and rs9332739 SNPs had both decreased correlations to AMD risk [15]. In a word, we should deep explore these partners of CFI gene, and gene-gene interactions in the development of AMD in the next step.…”

Section: Discussionmentioning

confidence: 99%

“…A dysfunctional complement pathway has been proposed to increase retinal cell damage via increased formation of drusen deposits, atrophy, and cell degeneration and progression to choroidal neovascularization (CNV) [13,14]. So far, component 2 (rs547154 and rs9332739) [15], component 5 [16], factor B (L9H) [17] and factor H (Y402H) [18] polymorphisms have been observed associated with AMD susceptibility. In 2015, our team first reported the association between component 3 gene polymorphisms and AMD risk…”

Section: Introductionmentioning

confidence: 99%

Complement family member CFI polymorphisms and AMD susceptibility from a comprehensive analysis

2020

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The complement factor I (CFI) gene polymorphisms have been reported to age-related macular degenerative (AMD) risk, nevertheless, above association is not consistent. We investigated a meta-analysis to evaluate the conclusions between CFI polymorphisms (rs10033900 and rs2285714) and AMD risk. An identification was covered with the PubMed and other databases through February 8, 2020. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations. After a comprehensive search, 11 different articles (12 case–control studies for total AMD and 11 case–control studies about neovascular disease/geographic atrophy in AMD) were retrieved. Individuals carrying C-allele or CC genotype of rs10033900 polymorphism may have a decreased risk to be AMD disease. For example, there has a significantly decreased relationship between rs10033900 polymorphism and AMD both in the whole group, Caucasian population and population-based source of control. Moreover, a similar trend in subgroup of genotype method group by MALDI-TOF MS was detected. To classify the type of AMD in further, decreased association was also observed in both neovascular disease and geographic atrophy AMD. No association was found about rs2285714 polymorphism. Our present groundbreaking study suggests that the CFI rs10033900 polymorphism is potentially associated with the risk of AMD development.

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“…A genome-wide association study (GWAS) showed a clearer view about significant links between AMD risk and genetic variations in 2005, suggesting AMD is a polygenic disease [10], which triggered numerous studies involving the genetic associations of AMD in the following 15 years [11][12][13]. So far, AMRS2 rs10490924 polymorphism, SNPs from complement factor H, C2/CFB, complement component C3, APOE haplotypes have been confirmed as being associated with susceptibility of AMD [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

High-temperature requirement factor A1 rs11200638 polymorphism and age-related macular degenerative from a comprehensive analysis about 15316 subjects

Liu¹,

Jin²,

Wei³

et al. 2020

Preprint

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Background The high-temperature requirement factor A1 (HTRA1) gene at the 10q26 locus has been associated with age-related macular degenerative (AMD) risk, with the significantly associated polymorphism being (rs11200638, -625G/A), however, above association is not consistent. We investigated an updated meta-analysis to evaluate the association between rs11200638 polymorphism and AMD risk thoroughly addressing this issue. Methods An identification was covered with the Pubmed and Chinese Wanfang databases through 27th Jan, 2020. Odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations. After a thorough and meticulous search, 35 different articles (33 case-control studies with HWE, 22 case-control studies about wet/dry AMD) were retrieved. Results Individuals carrying A-allele or AA genotype may have an increased risk to be AMD disease. For example, there has a significantly increased relationship between rs11200638 polymorphism and AMD both for Asians (OR: 2.50, 95%CI: 2.22-2.80 for A-allele vs. G-allele) and Caucasians (OR: 2.11, 95%CI: 1.43-3.13 for A-allele vs. G-allele). Moreover, a similar trend in the source of control subgroup was detected. To classify the type of AMD, increased association was also observed in both wet (OR: 3.40, 95%CI: 2.90-3.99 for dominant model) and dry (OR: 2.08, 95%CI: 1.24-3.48 for dominant model) AMD. Finally, based on the different genotyping methods, increased relationships were identified by sequencing, TaqMan, PCR-RFLP. Conclusions Our present meta-analysis suggests that the HTRA1 rs11200638 polymorphism are potentially associated with the risk of AMD development, especially about individuals carrying A-allele or AA genotype, who may be as identified targets to detect and intervene in advance. Further studies using larger sample sizes and including information about gene-environment interactions should be conducted to elucidate.

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Association Between Complement FactorC2/C3/CFB/CFHPolymorphisms and Age-Related Macular Degeneration: A Meta-Analysis

Cited by 29 publications

References 78 publications

Development and characterization of novel anti‐C5 monoclonal antibodies capable of inhibiting complement in multiple species

Development and characterization of novel anti‐C5 monoclonal antibodies capable of inhibiting complement in multiple species

Complement family member CFI polymorphisms and AMD susceptibility from a comprehensive analysis

High-temperature requirement factor A1 rs11200638 polymorphism and age-related macular degenerative from a comprehensive analysis about 15316 subjects

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