Genetic variant of C1GalT1 contributes to the susceptibility to IgA nephropathy.
BACKGROUND
IgA nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition that leads to mesangial proliferation and chronic glomerular inflammation. Analyses of serum IgA1 from IgAN patients revealed an abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may be a result of altered activity of core 1 beta1,3-galactosyltransferase (C1GalT1). To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case control study on cohorts from the Italian population.


METHODS
We sequenced C1GalT1 coding and promoter regions in 284 IgAN patients and 210 healthy controls. The functional role of 3' untranslated region (3'UTR) SNPs was studied using electrophoretic mobility shift assays and real-time quantitative PCR.


RESULTS
We analyzed 8 SNPs in the C1GalT1 gene: 5 SNPs were in the promoter region and 3 SNPs in the 3'UTR. The allele 1365G in the 3'UTR was significantly more frequent in IgAN patients than in healthy controls.


CONCLUSIONS
The 1365G allele and 1365G/G genotype seem to confer susceptibility to IgAN.
Pirulli
Doroti
D
Genetics Service, IRCCS Burlo Garofolo and Department of Reproductive and Developmental Sciences, University of Trieste, Trieste, Italy.
Crovella
Sergio
S
Ulivi
Sheila
S
Zadro
Cristina
C
Bertok
Sara
S
Rendine
Sabina
S
Scolari
Francesco
F
Foramitti
Marina
M
Ravani
Pietro
P
Roccatello
Dario
D
Savoldi
Silvana
S
Cerullo
Giuseppina
G
Lanzilotta
Salvatore Giovanni
SG
Bisceglia
Luigi
L
Zelante
Leopoldo
L
Floege
Jurgen
J
Alexopoulos
Epstathios
E
Kirmizis
Dimitrios
D
Ghiggeri
Gian Marco
GM
Frascà
Giovanni
G
Schena
Francesco Paolo
FP
Amoroso
Antonio
A
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005700:Galactosyltransferases / Q000097:blood / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007558:Italy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
D007070:Immunoglobulin A; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases