title: Interaction between ACE and ADD1 gene polymorphisms in the progression of IgA nephropathy in Japanese patients.
abstract: An interaction effect between the angiotensin-converting enzyme insertion/deletion (ACE I/D) and alpha-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; chi2=6.062, P=0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 (P=0.0016), but not for those with other ACE genotypes (hazard ratio=0.65, P=0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 757, Asahimachi-dori, Niigata, 951-8510, 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: Junya
authors.initials: J
authors.lastname: Ajiro
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sato
authors.forename: Daisuke
authors.initials: D
authors.lastname: Saga
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kondo
authors.forename: Kohei
authors.initials: K
authors.lastname: Akazawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakatsume
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
mesh_terms: D000328:Adult; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007564:Japan; D007674:Kidney Diseases / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D051780:Sterol Regulatory Element Binding Protein 1; D015996:Survival Rate; D014157:Transcription Factors
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D007703:Peptidyl-Dipeptidase A