|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Using a panel of 8854 SNPs associated with AAMD at p-values ≤5.0E-7 from a cohort of >30,000 elderly people, we identified SNPs in miRNA target-encoding constituents of: (1) regulator of complement activation (RCA) genes (rs390679, CFHR1, p≤2.14E-214 ; rs12140421, CFHR3, p≤4.63E-29); (2) genes of major histocompatibility complex (MHC) loci (rs4151672, CFB, p≤8.91E-41 ; rs115404146, HLA-C, p≤6.32E-12 ; rs1055821, HLA-B, p≤1.93E-9 ; rs1063355, HLA-DQB1, p≤6.82E-14); and (3) genes of the 10q26 AAMD locus (rs1045216, PLEKHA1, p≤4.17E-142 ; rs2672603, ARMS2, p≤7.14E-46).
|
28343170 |
2017 |
|
Age related macular degeneration
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
For example, CFHR1, most likely the main complement regulator in AMD pathogenesis was highly expressed in human RPE, but almost absent in mouse RPE.
|
26517551 |
2015 |
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
BEFREE |
We examined the triangular relationships of CFH/CFHR3/CFHR1 genotype, plasma CFH or CFHR1 concentrations and AMD susceptibility in combined case-control (1256 cases, 1020 controls) and cross-sectional population (n = 1004) studies and carried out genome-wide association studies of plasma CFH and CFHR1 concentrations.
|
23873044 |
2013 |
|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Seventeen single nucleotide polymorphisms (SNPs) in known AMD risk-associated genes including CFH (rs800292, rs3766404, rs1061170, rs2274700 and rs393955), HTRA1 (rs11200638), CFHR1-5 (rs10922153, rs16840639, rs6667243, and rs1853883), LOC387715/ARMS2 (rs3793917 and rs10490924), C3 (rs2230199 and rs1047286), C2 (rs547154), CFB (rs641153) and F13B (rs6003) were examined.
|
23582991 |
2013 |
|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
GWASDB |
Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.
|
23326517 |
2013 |
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
BEFREE |
The results support a relevant role of CFHR1 in the pathogenesis of AMD.
|
22247456 |
2012 |
|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Combined deletion of CFHR3 and CFHR1 was associated with a decreased risk of developing AMD.
|
21850184 |
2011 |
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
BEFREE |
Additionally, 698 CNPs showed significant differences with false discovery rate (FDR)<0.01 among the 10 populations and these loci overlap with known disease-associated or pharmacogenetic-related genes such as CFHR3 and CFHR1 (age related macular degeneration), GSTTI (metabolism of various carcinogenic compounds and cancers) and UGT2B17 (prostate cancer and graft-versus-host disease).
|
21677662 |
2011 |
|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
This study showed that CFH was more likely to be AMD susceptibility gene at Chr.1q31 based on the finding that the CFHR1 and CFHR3 deletion was not polymorphic in the cohort of this study, and none of the SNPs that were significantly associated with AMD in a white population in C2, CFB, and C3 genes showed a significant association with AMD.
|
20523265 |
2010 |
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
BEFREE |
Thus, deficiency of CFHR3 and CFHR1 results in a loss of complement control but enhances local regulation by factor H. Our findings allude to a critical balance between the complement regulators CFHR3, CFHR1 and factor H and further emphasize the central role of complement regulation in AMD pathology.
|
20843825 |
2010 |
|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Subsequently, genetic studies revealed highly significant statistical associations between AMD and variants of several complement pathway-associated genes including: Complement factor H (CFH), complement factor H-related 1 and 3 (CFHR1 and CFHR3), complement factor B (CFB), complement component 2 (C2), and complement component 3 (C3).
|
19961953 |
2010 |
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
BEFREE |
However deletion of a chromosomal segment in the Factor H gene cluster on human chromosome 1, which results in the deficiency of the terminal pathway regulator CFHR1, and of the putative complement regulator CFHR3 has a protective effect for development of AMD.
|
20711704 |
2010 |
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
BEFREE |
Deletion of CFHR3 and CFHR1 protected against the development of AMD at least in part because the deletion tagged a protective haplotype and did not occur on the risk haplotype.
|
19553609 |
2009 |
|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
LHGDN |
Recently, deletion of the 'CFH-related' genes CFHR1 and CFHR3 was found to be segregating with a particular CFH haplotype, which reduced the risk of AMD.
|
18084039 |
2008 |
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
BEFREE |
We here summarize the current knowledge about the role or association of CFHR1 and CFHR3 in the human diseases HUS and AMD.
|
19388158 |
2008 |
|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Recently, deletion of the 'CFH-related' genes CFHR1 and CFHR3 was found to be segregating with a particular CFH haplotype, which reduced the risk of AMD.
|
18084039 |
2008 |
|
Age related macular degeneration
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration.
|
16998489 |
2006 |
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
|
|
|
|
Age related macular degeneration
|
0.500 |
Biomarker
|
disease |
HPO |
|
|
|
|
Atypical Hemolytic Uremic Syndrome
|
0.400 |
Biomarker
|
disease |
BEFREE |
"Supercontrols" are more informative than general population because they share at least one risk factor (FHR1 deficiency) with aHUS patients.
|
31118930 |
2019 |
|
Atypical Hemolytic Uremic Syndrome
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
A retrospective genetic analysis in our aHUS cohort (<i>n</i>=513) using multiple ligation probe amplification uncovered nine unrelated patients carrying a genetic abnormality in the complement factor H related 1 gene (<i>CFHR1</i>) that originates by recurrent gene conversion events between the <i>CFH</i> and <i>CFHR1</i> genes.
|
28993505 |
2018 |
|
Atypical Hemolytic Uremic Syndrome
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
We have previously shown that haplotype <i>CFH(H3)-CFHR3*B-CFHR1*B</i> associates with aHUS and reduced FH levels.
|
29740447 |
2018 |
|
Atypical Hemolytic Uremic Syndrome
|
0.400 |
Biomarker
|
disease |
BEFREE |
Our data suggest a complex matrix of interactions between FHR1-FHR3 deletion, immunomodulation and anti-FH autoantibodies in the aetiopathogenesis of aHUS.
|
29485195 |
2018 |
|
Atypical Hemolytic Uremic Syndrome
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
Genetic analysis showed large heterozygous deletion encompassing the entire CFHR1 and CFHR3, a finding previously associated with patients presenting atypical hemolytic-uremic syndrome (aHUS).
|
28905254 |
2017 |
|
Atypical Hemolytic Uremic Syndrome
|
0.400 |
Biomarker
|
disease |
BEFREE |
We observed a similar extent of autoantibody binding to the aHUS-specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite seven of our patients being deficient for CFHR1.
|
28424685 |
2017 |