Genetic heterogeneity in Italian families with IgA nephropathy: Suggestive linkage for two novel IgA nephropathy loci

Luigi Bisceglia, Giuseppina Cerullo, Paola Forabosco, Diletta Domenica Torres, Francesco Scolari, Michele Di Perna, Marina Foramitti, Antonio Amoroso, Sara Bertok, Jürgen Floege, Peter Rene Mertens, Klaus Zerres, Efstathios Alexopoulos, Dimitrios Kirmizis, Mazzucco Ermelinda, Leopoldo Zelante, Francesco Paolo Schena

Research output: Contribution to journalArticlepeer-review

Abstract

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, but its etiologic mechanisms are still poorly understood. Different prevalences among ethnic groups and familial aggregation, together with an increased familial risk, suggest important genetic influences on its pathogenesis. A locus for familial IgAN, called "IGAN1," on chromosome 6q22-23 has been described, without the identification of any responsible gene. The partners of the European IgAN Consortium organized a second genomewide scan in 22 new informative Italian multiplex families. A total of 186 subjects (59 affected and 127 unaffected) were genotyped and were included in a two-stage genomewide linkage analysis. The regions 4q26-31 and 17q12-22 exhibited the strongest evidence of linkage by nonparametric analysis (best P = .0025 and .0045, respectively). These localizations were also supported by multipoint parametric analysis, in which peak LOD scores of 1.83 (α = 0.50) and 2.56 (α = 0.65) were obtained using the affected-only dominant model, and by allowance for the presence of genetic heterogeneity. Our results provide further evidence for genetic heterogeneity among families with IgAN. Evidence of linkage to multiple chromosomal regions is consistent with both an oligo/polygenic and a multiple-susceptibility-gene model for familial IgAN, with small or moderate effects in determining the pathological phenotype. Although we identified new candidate-regions, replication studies are required to confirm the genetic contribution to familial IgAN.

Original languageEnglish
Pages (from-to)1130-1134
Number of pages5
JournalAmerican Journal of Human Genetics
Volume79
Issue number6
DOIs
Publication statusPublished - Dec 2006

ASJC Scopus subject areas

  • Genetics

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