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  • Title: The CTLA-4 +49GG genotype is associated with susceptibility for nephrotic kidney diseases.
    Author: Spink C, Stege G, Tenbrock K, Harendza S.
    Journal: Nephrol Dial Transplant; 2013 Nov; 28(11):2800-5. PubMed ID: 23975748.
    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.
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