title: Search for genetic association between IgA nephropathy and candidate genes selected by function or by gene mapping at loci IGAN2 and IGAN3.
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.
authors: Transplantation Immunology Service, San Giovanni Battista University Hospital, Turin, Italy. francesca.bertinetto@unito.it
authors: Francesca Eleonora
authors: FE
authors: Bertinetto
authors: Francesc
authors: F
authors: Calafell
authors: Stefano
authors: S
authors: Roggero
authors: Rossella
authors: R
authors: Chidichimo
authors: Elena
authors: E
authors: Garino
authors: Cristina
authors: C
authors: Marcuccio
authors: Rosanna
authors: R
authors: Coppo
authors: Francesco
authors: F
authors: Scolari
authors: Giovanni Maria
authors: GM
authors: Frascá
authors: Silvana
authors: S
authors: Savoldi
authors: Francesco Paolo
authors: FP
authors: Schena
authors: Antonio
authors: A
authors: Amoroso
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011507:Proteinuria / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D015415:Biomarkers