title: Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci.
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 ( alpha =0.50) and 2.56 ( alpha =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.
authors.affiliation: Medical Genetic Service, IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bisceglia
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Cerullo
authors.forename: Paola
authors.initials: P
authors.lastname: Forabosco
authors.forename: Diletta Domenica
authors.initials: DD
authors.lastname: Torres
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Michele
authors.initials: M
authors.lastname: Di Perna
authors.forename: Marina
authors.initials: M
authors.lastname: Foramitti
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.forename: Sara
authors.initials: S
authors.lastname: Bertok
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Peter Rene
authors.initials: PR
authors.lastname: Mertens
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.forename: Efstathios
authors.initials: E
authors.lastname: Alexopoulos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kirmizis
authors.forename: Mazzucco
authors.initials: M
authors.lastname: Ermelinda
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Schena
mesh_terms: D000293:Adolescent; D000328:Adult; D002877:Chromosomes, Human; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010375:Pedigree