Is complement factor H a susceptibility factor for IgA nephropathy?
There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of IgA nephropathy. Mesangial C3 deposition is seen in approximately 90% of patients and polymeric IgA has been shown to activate the alternative and lectin pathways. In addition there have been reports of deficiency and mutations in the serum complement regulator factor H (CFH) in association with IgA nephropathy. In this study we have examined the hypothesis that CFH is a susceptibility factor for IgA nephropathy. In 46 IgA nephropathy patients we undertook genotyping of three CFH SNPS (rs3753394, rs3753396 and rs1065489). There was no significant difference in the allele frequency of these 3 SNPs between the patients and normal controls. In the same group of patients we undertook mutation screening of CFH exons 18-23 using direct sequencing and found no abnormalities. All the patients had a normal serum factor H concentration. In this small cohort of IgA nephropathy patients we have not found evidence to support the hypothesis that factor H is a major susceptibility factor for the disease.
Edey
Matthew
M
Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK.
Strain
Lisa
L
Ward
Roy
R
Ahmed
Saeed
S
Thomas
Trevor
T
Goodship
Timothy H J
TH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D015331:Cohort Studies; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D017242:Complement Factor H / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D055815:Young Adult
C493495:CFH protein, human; D003176:Complement C3; D003181:Complement C4; D017242:Complement Factor H