title: FcgammaRIIa-131R allele and FcgammaRIIIa-176V/V genotype are risk factors for progression of IgA nephropathy.
abstract: BACKGROUND
  Fcgamma receptors (FcgammaRs) may play an important role in positive and negative regulation of immune cell responses and immune complex (IC) clearance. Mesangial IgG deposition and circulating IgG/IgA-IC in sera are observed in patients with IgA nephropathy (IgAN). Therefore, the pathological roles of IgG-IC in IgAN have been discussed. On the other hand, several studies have identified FcgammaR polymorphisms (FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb) that determine susceptibility to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The objective of the present study was to clarify whether FcgammaR polymorphisms influence susceptibility to IgAN, clinical features or severity in patients with IgAN.
  
  
  METHODS
  Japanese patients with IgAN (n = 124) and healthy controls (n = 100) were genotyped for FcgammaR polymorphisms (FcgammaRIIa-131H or R, FcgammaRIIIa-176F or V and FcgammaRIIIb-NA1 or -NA2). The genotyping of these polymorphisms was performed using allele-specific polymerase chain reaction (PCR) methods. Associations among FcgammaR polymorphisms and susceptibility, age of onset, levels of serum immunoglobulins, intensity of glomerular IgG deposition and pathological severity were analysed.
  
  
  RESULTS
  These three FcgammaR polymorphisms showed no significant differences in genotype and allele frequencies between the IgAN patients and healthy controls. Each FcgammaR polymorphism had no influence on age of onset, serum levels of IgG and glomerular IgG deposition in IgAN. However, FcgammaRIIa-131R (R/R or H/R) or FcgammaRIIIa-176V homozygous carriers (V/V) showed significantly more severe injury than FcgammaRIIa-131H homozygous (H/H) (P < 0.03) or FcgammaRIIIa-176F carriers (F/F or F/V) (P < 0.03), respectively.
  
  
  CONCLUSIONS
  The present study shows that polymorphisms of FcgammaRIIa and FcgammaRIIIa influence the severity of IgAN in Japanese patients but not the incidence, suggesting that IgG-IC may play important roles in the progression and prognosis of this disease via FcgammaRs.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Toshinao
authors.initials: T
authors.lastname: Tsuge
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kanamaru
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D005819:Genetic Markers; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015703:Antigens, CD; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; D005819:Genetic Markers; D017452:Receptors, IgG; D004247:DNA