title: Genetic polymorphism of NPHS1 modifies the clinical manifestations of Ig A nephropathy.
abstract: Nephrin, the molecule responsible for congenital nephrotic syndrome of Finnish type, is crucial in maintaining the glomerular filtration barrier. Recently, its complete gene structure and common gene polymorphisms in its exons have been reported, although the functional and clinical significance of these polymorphisms has not yet been elucidated. We investigated a possible association of the NPHS1 polymorphisms with the development of Ig A nephropathy (IgAN), as well as the clinical and histologic manifestations in IgAN. A total of 464 Japanese subjects, including 267 patients with histologically proven IgAN and 197 healthy controls with normal urinalysis, were genotyped for the NPHS1 G349A, G2289A, and T3315C polymorphisms. The frequencies of the genotypes, alleles, and estimated haplotypes of NPHS1 polymorphisms were no different between patients with IgAN and the controls. Within the IgAN group, patients carrying at least one G allele of G349A tended to present with more proteinuria, lower renal function, and more severe histopathologic injury than those with the AA genotype, although the time from the first urinary abnormality to the renal biopsy was no different between both groups. The logistic regression analysis indicated that even after adjusting for the effect of proteinuria and hypertension the GG genotype of NPHS1 G349A was an independent risk factor for the deteriorated renal function at the time of diagnosis. This study suggests that the NPHS1 G349A polymorphism may be associated with heavy proteinuria and a decline in renal function in patients with IgAN.
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan. naritai@med.niigata-u.ac.jp
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.forename: Shin
authors.initials: S
authors.lastname: Goto
authors.forename: Noriko
authors.initials: N
authors.lastname: Saito
authors.forename: Jin
authors.initials: J
authors.lastname: Song
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kondo
authors.forename: Kentaro
authors.initials: K
authors.lastname: Omori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Fujio
authors.initials: F
authors.lastname: Shimizu
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakatsume
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ueno
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005921:Glomerulonephritis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin