Journal
NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 28, Issue 11, Pages 2800-2805Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gft381
Keywords
CTLA-4; focal segmental glomerulosclerosis; membranous nephropathy; minimal-change disease; single-nucleotide polymorphism
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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. 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. 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 1.7486.622, OR 3.846, 95 CI 1.9457.604 and OR 2.381, 95 CI 1.2574.511, respectively). No further significant associations, neither with the heterozygous genotype of 49A/G nor for the 318C/T or CT60 SNP, were detected. 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.
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