TORNA ALL’ELENCO

Search for genetic association between IgA nephropathy and candidate genes selected by function or by gene mapping at loci IGAN2 and IGAN3 in Nephrology Dialysis Transplantation

2012
ASL Torino 4

Tipo pubblicazione

Article

Autori/Collaboratori (12)Vedi tutti...

Bertinetto FE
RSA Villa Serena, Bologna (BO), Italy
Calafell F
RSA Villa Serena, Bologna (BO), Italy
Roggero S
RSA Villa Serena, Bologna (BO), Italy

et alii...

Abstract

Background. IgA nephropathy (IgAN) is not generally considered a hereditary disease, even though extensive evidence suggests an undefined genetic influence. Linkage analysis identified a number of genome regions that could contain variations linked to IgAN.Methods.In this case-control association study, genes possibly involved in the development of IgAN were investigated. DNA samples from 460 North Italian patients with IgAN and 444 controls were collected. Candidate genes were selected based on their possible functional involvement (6 genes) or because of their location within linkage-identified genomic regions IGAN2 and IGAN3 (5 and 13 genes within chromosome 4q26-31 and 17q12-22, respectively). One hundred and ninety-two tag and functional single-nucleotide polymorphisms (SNPs) were typed with Veracode GoldenGate technology (Illumina).Results.C1GALT1 showed an association with IgAN (rs1008898: P = 0.0019 and rs7790522: P = 0.0049). Associations were found when the population was stratified by gender (C1GALT1, CD300LG, GRN, ITGA2B, ITGB3 in males and C1GALT1, TRPC3, B4GALNT2 in females) and by age (TLR4, ITGB3 in patients aged <27 years). Furthermore, rs7873784 in TLR4 showed an association with proteinuria (G allele: P = 0.0091; GG genotype: P = 0.0077).Conclusions.Age and gender are likely to evidence distinct immunological and inflammatory reactions leading to individual susceptibility to IgAN. Overall, a genetic predisposition to sporadic IgAN was found. We might hypothesize that C1GALT1 and TLR4 polymorphisms influence the risk to develop IgAN and proteinuria, respectively. © 2012 The Author.

PMID : 22131235

DOI : 10.1093/ndt/gfr633

Keywords

genetic susceptibility; genetic predisposition; genetic association; gene mapping; gene locus; gene function; gender; female; controlled study; chromosome 4q; chromosome 17q; case control study; article; age; adult; unclassified drug; transient receptor potential channel 3; toll like receptor 4; sialyltransferase; protein; peptidase; nephronectin; interleukin 21; immunoglobulin A; galactosyltransferase; Fc receptor; Fc alpha receptor; DNA; complement factor I; chaperone; CD71 antigen; beta 1,3 galactosyltransferase; aminopeptidase A ectopeptidase; 1 beta 3 galactosyltransferase; human; immunoglobulin A nephropathy; immunopathology; inflammation; Italy; kidney transplantation; major clinical study; male; priority journal; proteinuria; risk assessment; single nucleotide polymorphism;