The Association Between Complement Component 2/Complement Factor B
          Polymorphisms and Age-related Macular Degeneration: A HuGE Review and
          Meta-Analysis

Objective: To investigate the potential correlation between complement factor B polymorphisms and age-related macular degeneration. Methods: We retrieved relevant articles systematically by searching PubMed and Web of Science databases. The pooled odds ratios and 95% confidence intervals were calculated for five complement factor B polymorphism rs641153, rs4151667, rs1048709, rs2072633, and rs12614 using data from included articles in both random effects and fixed effect models. Subgroup meta-analysis based on age-related macular degeneration type, choroidal neovascular disease (rs641153 and rs4151667), geographic atrophy (rs641153 and rs4151667), and races was also performed. Results: In the overall comparison, we observed that the distribution of rs641153 and the risk of age-related macular degeneration were significantly correlated (p < 0.00001). Similar results were obtained in subgroup analysis based on race (Caucasians, p < 0.00001; Asians, p = 0.003) and age-related macular degeneration type (choroidal neovascular disease, p < 0.00001; geographic atrophy, p = 0.04). As for complement factor B rs4151667, the genotypic effects were also demonstrated statistically significant in overall analysis (p < 0.00001) and only in Caucasians diagnosed with choroidal neovascular disease (p = 0.004), but not in Asians. Moreover, no statistically significant correlations between the complement factor B polymorphisms rs1048709 (p = 0.63), rs2072633 (p = 0.72), rs12614 (p = 0.98) and susceptibility to age-related macular degeneration were detected in either overall or subgroup analysis. Conclusion: Collectively, we demonstrated that the complement factor B genes rs641153 and rs4151667, but not rs1048709, rs2072633, rs12614, were associated with the susceptibility of age-related macular degeneration and might play predictive roles in future age-related macular degeneration diagnosis. More studies are needed to verify these findings.

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Complement Factor B Polymorphism and the Phenotype of Early Age-related Macular Degeneration

Ophthalmic Genetics ◽

10.3109/13816810.2013.766217 ◽

2013 ◽

Vol 35 (1) ◽

pp. 12-17 ◽

Cited By ~ 9

Author(s):

Irmela Mantel ◽

Aude Ambresin ◽

Leila Moetteli ◽

Ivaine Droz ◽

Raphaël Roduit ◽

...

Keyword(s):

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Early Age ◽

Complement Factor ◽

Factor B ◽

Complement Factor B ◽

Age Related

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The effect of complement factor B gene variation on age-related macular degeneration in Iranian patients

Journal of Current Ophthalmology ◽

10.1016/j.joco.2019.07.005 ◽

2019 ◽

Vol 31 (3) ◽

pp. 292-297

Author(s):

Nasrin Roshanipour ◽

Morteza Bonyadi ◽

Mohammad Hossein Jabbarpour Bonyadi ◽

Masoud Soheilian

Keyword(s):

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Complement Factor ◽

Factor B ◽

Complement Factor B ◽

Gene Variation ◽

Age Related ◽

Iranian Patients

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Functional basis of protection against age-related macular degeneration conferred by a common polymorphism in complement factor B

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0812584106 ◽

2009 ◽

Vol 106 (11) ◽

pp. 4366-4371 ◽

Cited By ~ 77

Author(s):

T. Montes ◽

A. Tortajada ◽

B. P. Morgan ◽

S. Rodriguez de Cordoba ◽

C. L. Harris

Keyword(s):

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Complement Factor ◽

Factor B ◽

Complement Factor B ◽

Functional Basis ◽

Common Polymorphism ◽

Age Related

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Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽

10.3390/biology10070622 ◽

2021 ◽

Vol 10 (7) ◽

pp. 622

Author(s):

Iswariyaraja Sridevi Gurubaran ◽

Hanna Heloterä ◽

Stephen Marry ◽

Ali Koskela ◽

Juha M. T. Hyttinen ◽

...

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Macular Degeneration ◽

Complement Component ◽

Factor H ◽

Age Related Macular Degeneration ◽

Related Factor ◽

Complement Factor ◽

Age Related ◽

Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

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Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2019-000361 ◽

2020 ◽

Vol 5 (1) ◽

pp. e000361 ◽

Cited By ~ 1

Author(s):

Anne M Lynch ◽

Alan G Palestine ◽

Brandie D Wagner ◽

Jennifer L Patnaik ◽

Ashley A Frazier-Abel ◽

...

Keyword(s):

Macular Degeneration ◽

Factor H ◽

Age Related Macular Degeneration ◽

Complement Factor ◽

Factor B ◽

Complement Factors ◽

Factor I ◽

Reticular Pseudodrusen ◽

Age Related ◽

Complement Dysregulation

ObjectiveSystemic activation of the complement system in intermediate age-related macular degeneration (AMD) is understudied. Moreover, links between the presence of reticular pseudodrusen (RPD) and systemic complement dysregulation have not been studied. The aim of this study was to determine if there is a difference in plasma complement factor levels in intermediate AMD compared with controls, and if complement levels are related to the presence of RPD.Methods and analysisLevels of complement factors C1q (µg/mL), C4 (µg/mL), C2 (µg/mL), Mannose Binding Lectin (ng/mL), C4b (µg/mL), C3 (µg/mL), factor B (µg/mL), factor D (µg/mL), properdin (µg/mL), C3a (ng/mL), iC3b/C3b (ng/mL), Ba (ng/mL), factor H (µg/mL), factor I (µg/mL), C5 (µg/mL), C5a (pg/mL) and SC5b-9 (ng/mL) were measured in plasma.Results109 cases and 65 controls were included in the study. Thirty-nine (36%) cases had RPD. Significantly lower systemic levels of: C1q (OR 0.96, 95% CI 0.94 to 0.98), factor B (OR 0.98, 95% CI 0.96 to 0.99), iC3b/C3b (OR 0.97, 95% CI 0.95 to 0.98), factor H (OR 0.99, 95% CI 0.98 to 0.99), factor I (OR 0.83, 95% CI 0.77 to 0.89) and C5 (OR 0.94, 95% CI 0.90 to 0.98) were found in cases versus controls. Significantly elevated levels of: C2 (OR 1.29, 95% CI 1.07 to 1.59), C3a (OR 1.03, 95% CI 1.01 to 1.05) Ba (OR 1.03, 95% CI 1.01 to 1.05) and C5a (OR 1.04, 95% CI 1.02 to 1.07) were found in cases versus controls. Systemic levels of complement factors measured were not related to the presence of RPD.ConclusionsLevels of several systemic complement pathway factors were found to be altered in intermediate AMD. Systemic levels of complement factors were not related to RPD.

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