Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 215.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 249.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26825529
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2016 ; 27
(9
): 2894-905
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Rare Variants in the Complement Factor H-Related Protein 5 Gene Contribute to
Genetic Susceptibility to IgA Nephropathy
#MMPMID26825529
Zhai YL
; Meng SJ
; Zhu L
; Shi SF
; Wang SX
; Liu LJ
; Lv JC
; Yu F
; Zhao MH
; Zhang H
J Am Soc Nephrol
2016[Sep]; 27
(9
): 2894-905
PMID26825529
show ga
A recent genome-wide association study of IgA nephropathy (IgAN) identified 1q32,
which contains multiple complement regulatory genes, including the complement
factor H (CFH) gene and the complement factor H-related (CFHRs) genes, as an IgAN
susceptibility locus. Abnormal complement activation caused by a mutation in
CFHR5 was shown to cause CFHR5 nephropathy, which shares many characteristics
with IgAN. To explore the genetic effect of variants in CFHR5 on IgAN
susceptibility, we recruited 500 patients with IgAN and 576 healthy controls for
genetic analysis. We sequenced all exons and their intronic flanking regions as
well as the untranslated regions of CFHR5 and compared the frequencies of
identified variants using the sequence kernel association test. We identified 32
variants in CFHR5, including 28 rare and four common variants. The distribution
of rare variants in CFHR5 in patients with IgAN differed significantly from that
in controls (P=0.002). Among the rare variants, in silico programs predicted nine
as potential functional variants, which we then assessed in functional assays.
Compared with wild-type CFHR5, three recombinant CFHR5 proteins, CFHR5-M
(c.508G>A/p.Val170Met), CFHR5-S (c.533A>G/p.Asn178Ser), and CFHR5-D
(c.822A>T/p.Glu274Asp), showed significantly higher C3b binding capacity
(CFHR5-M: 109.67%±3.54%; P=0.02; CFHR5-S: 174.27%±9.78%; P<0.001; CFHR5-D:
127.25%±1.75%; P<0.001), whereas another recombinant CFHR5
(c.776T>A/p.Leu259Termination) showed less C3b binding (56.89%±0.57%; P<0.001).
Our study found that rare variants in CFHR5 may contribute to the genetic
susceptibility to IgAN, which suggests that CFHR5 is an IgAN susceptibility gene.