title: The CTLA-4 +49GG genotype is associated with susceptibility for nephrotic kidney diseases.
abstract: BACKGROUND
  The pathogenesis of primary nephrotic kidney diseases is not completely understood. As T-cell involvement is suspected, cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed on activated T cells could play a role in the immune response. Single-nucleotide polymorphisms (SNPs) in the CTLA-4 gene are associated with several autoimmune-related diseases.
  
  
  METHODS
  Our goal was to study the occurrence of the SNPs -318C/T, +49A/G and CT60 on the CTLA-4 gene in healthy blood donors (N = 156) compared with nephrotic patients with biopsy-proven minimal-change disease (MCD, N = 160), focal segmental glomerulosclerosis (FSGS, N = 159) and membranous nephropathy (MN, N = 185). Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the strength of the association.
  
  
  RESULTS
  The +49GG genotype was significantly (P < 0.001) associated with the risk for MCD, FSGS and MN (AA versus GG: OR = 3.403, 95% CI = 1.748-6.622, OR = 3.846, 95% CI = 1.945-7.604 and OR = 2.381, 95% CI = 1.257-4.511, respectively). No further significant associations, neither with the heterozygous genotype of +49A/G nor for the -318C/T or CT60 SNP, were detected.
  
  
  CONCLUSIONS
  The +49GG genotype of the +49A/G SNP in the CTLA-4 gene is associated with the risk for MCD, FSGS and MN, suggesting a possible role for CTLA-4 in a proposed common final pathway in the pathogenesis of primary nephrotic kidney diseases.
authors: Zentrum für Innere Medizin, III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors: Clemens
authors: C
authors: Spink
authors: Gesa
authors: G
authors: Stege
authors: Klaus
authors: K
authors: Tenbrock
authors: Sigrid
authors: S
authors: Harendza
mesh_terms: D000328:Adult; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015433:Glomerulonephritis, Membranous / Q000235:genetics*; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: CTLA-4; focal segmental glomerulosclerosis; membranous nephropathy; minimal-change disease; single-nucleotide polymorphism