Variation in complement factor H affects complement activation in immunoglobulin A vasculitis with nephritis.
Adult
Case-Control Studies
Complement Activation
/ genetics
Complement C3
/ metabolism
Complement Factor H
/ genetics
Female
Gene Frequency
Genetic Predisposition to Disease
Glomerulonephritis, IGA
/ blood
Humans
Kidney
/ immunology
Male
Phenotype
Polymorphism, Single Nucleotide
Vasculitis
/ blood
Young Adult
IgA nephropathy
complement activation
complement factor H
immunoglobulin A vasculitis with nephritis
Journal
Nephrology (Carlton, Vic.)
ISSN: 1440-1797
Titre abrégé: Nephrology (Carlton)
Pays: Australia
ID NLM: 9615568
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
accepted:
26
02
2019
pubmed:
7
3
2019
medline:
2
6
2020
entrez:
7
3
2019
Statut:
ppublish
Résumé
Immunoglobulin A (IgA) vasculitis with nephritis (IgAVN) and IgA nephropathy (IgAN) are widely considered as related diseases. Considerable evidences support the notion of involvement of complement activation in both IgAVN and IgAN. Our previous studies identified a genetic variant in complement factor H (CFH), rs6677604, as an IgAN-susceptible variant by genome-wide association study, and further confirmed its linkage to CFHR3-1Δ and proved its influence on complement activation and thereby on IgAN susceptibility. To explore the role of rs6677604 in complement activation of IgAVN. In this study, we enrolled 632 patients with IgAVN, 1178 patients with IgAN and 902 healthy controls. The genotype of rs6677604 was measured by TaqMan allele discrimination assays or was extracted from genome-wide association study data. The frequency of the rs6677604-A allele was significantly higher in IgAVN than in IgAN. However, no significant differences were observed between IgAVN and the controls. Higher complement factor H (FH) levels were observed in IgAVN than IgAN, and positive correlation between circulating FH and C3 levels was present in IgAVN. In both IgAVN and IgAN, rs6677604-A was associated with less intensity of glomerular C3 deposits. In agreement with the higher frequency of rs6677604-A in IgAVN, the glomerular C3 deposits of patients with IgAVN were less intense than those in IgAN. Our findings suggest that genetic variation in CFH (rs6677604) is involved in the phenotype of complement activation in both IgAVN and IgAN. Moreover, rs6677604 might contribute to the difference of complement activation intensity between IgAVN and IgAN.
Sections du résumé
BACKGROUND
BACKGROUND
Immunoglobulin A (IgA) vasculitis with nephritis (IgAVN) and IgA nephropathy (IgAN) are widely considered as related diseases. Considerable evidences support the notion of involvement of complement activation in both IgAVN and IgAN. Our previous studies identified a genetic variant in complement factor H (CFH), rs6677604, as an IgAN-susceptible variant by genome-wide association study, and further confirmed its linkage to CFHR3-1Δ and proved its influence on complement activation and thereby on IgAN susceptibility.
AIM
OBJECTIVE
To explore the role of rs6677604 in complement activation of IgAVN.
METHODS
METHODS
In this study, we enrolled 632 patients with IgAVN, 1178 patients with IgAN and 902 healthy controls. The genotype of rs6677604 was measured by TaqMan allele discrimination assays or was extracted from genome-wide association study data.
RESULTS
RESULTS
The frequency of the rs6677604-A allele was significantly higher in IgAVN than in IgAN. However, no significant differences were observed between IgAVN and the controls. Higher complement factor H (FH) levels were observed in IgAVN than IgAN, and positive correlation between circulating FH and C3 levels was present in IgAVN. In both IgAVN and IgAN, rs6677604-A was associated with less intensity of glomerular C3 deposits. In agreement with the higher frequency of rs6677604-A in IgAVN, the glomerular C3 deposits of patients with IgAVN were less intense than those in IgAN.
CONCLUSION
CONCLUSIONS
Our findings suggest that genetic variation in CFH (rs6677604) is involved in the phenotype of complement activation in both IgAVN and IgAN. Moreover, rs6677604 might contribute to the difference of complement activation intensity between IgAVN and IgAN.
Substances chimiques
C3 protein, human
0
CFH protein, human
0
Complement C3
0
Complement Factor H
80295-65-4
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
40-47Subventions
Organisme : National Natural Science Foundation of China
ID : 81670638
Organisme : the Natural Science Foundation for Innovation Research Group of China
ID : 81621092
Organisme : the National Key Research and Development Program of China
ID : 2016YFC0904102
Organisme : Beijing New-Star Plan of Science and Technology
ID : Z161100004916167
Organisme : the Training Program of the Major Research Plan of the National Natural Science Foundation of China
ID : 91642120
Informations de copyright
© 2019 Asian Pacific Society of Nephrology.
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