CTLA-4 Polymorphisms in Patients with IgA Nephropathy Correlate with Proteinuria
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CTLA-4 Polymorphisms in Patients with IgA Nephropathy Correlate with Proteinuria. / Jacob, Marius; Ohl, Kim; Goodarzi, Tannaz; Harendza, Sigrid; Eggermann, Thomas; Fitzner, Christina; Hilgers, Ralf-Dieter; Bolte, Anna; Floege, Jürgen; Rauen, Thomas; Tenbrock, Klaus.
in: KIDNEY BLOOD PRESS R, Jahrgang 43, Nr. 2, 2018, S. 360-366.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - CTLA-4 Polymorphisms in Patients with IgA Nephropathy Correlate with Proteinuria
AU - Jacob, Marius
AU - Ohl, Kim
AU - Goodarzi, Tannaz
AU - Harendza, Sigrid
AU - Eggermann, Thomas
AU - Fitzner, Christina
AU - Hilgers, Ralf-Dieter
AU - Bolte, Anna
AU - Floege, Jürgen
AU - Rauen, Thomas
AU - Tenbrock, Klaus
N1 - © 2018 The Author(s). Published by S. Karger AG, Basel.
PY - 2018
Y1 - 2018
N2 - BACKGROUND/AIMS: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and still constitutes one of the most important causes of end-stage renal disease. Abnormal T cell responses may play a role in IgAN pathogenesis. Co-stimulatory molecules such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are important for naive T cells to initiate and terminate immune responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 gene locus are associated with several autoimmune diseases.METHODS: We aimed to investigate the occurrence of the SNPs -318C/T, +49A/G and CT60 G/A within the CTLA4 locus in healthy blood donors (n=455) and IgAN patients (n=252) recruited from the recently published STOP-IgAN trial. The presence of these SNPs was then associated with baseline proteinuria in IgAN patients.RESULTS: We observed a significantly increased frequency of the CTLA4 -318C/T genotype in IgAN patients as compared to controls (CC vs. CT+TT: OR 1.65, 95%-CI 1.03-2.65, p=0.035). No significant associations, neither with the +49A/G nor for the CT60 G/A SNP, were detected. However, when we stratified for proteinuria at time of inclusion into the STOP-IgAN trial (<1 g/day vs. >1 g/day), we observed significant differences in the frequencies of the CT60 G/A genotype, i.e. a significantly increased risk for higher proteinuria in patients carrying the G allele (OR 2.81, 95%-CI 1.03-7.64, p=0.042).CONCLUSION: The CTLA4 -318/C/T SNP was associated with an increased risk to develop IgAN, while the CT60 G/A genotype significantly associated with the risk for higher proteinuria suggesting a possible role for CTLA-4 in IgAN.
AB - BACKGROUND/AIMS: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and still constitutes one of the most important causes of end-stage renal disease. Abnormal T cell responses may play a role in IgAN pathogenesis. Co-stimulatory molecules such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are important for naive T cells to initiate and terminate immune responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 gene locus are associated with several autoimmune diseases.METHODS: We aimed to investigate the occurrence of the SNPs -318C/T, +49A/G and CT60 G/A within the CTLA4 locus in healthy blood donors (n=455) and IgAN patients (n=252) recruited from the recently published STOP-IgAN trial. The presence of these SNPs was then associated with baseline proteinuria in IgAN patients.RESULTS: We observed a significantly increased frequency of the CTLA4 -318C/T genotype in IgAN patients as compared to controls (CC vs. CT+TT: OR 1.65, 95%-CI 1.03-2.65, p=0.035). No significant associations, neither with the +49A/G nor for the CT60 G/A SNP, were detected. However, when we stratified for proteinuria at time of inclusion into the STOP-IgAN trial (<1 g/day vs. >1 g/day), we observed significant differences in the frequencies of the CT60 G/A genotype, i.e. a significantly increased risk for higher proteinuria in patients carrying the G allele (OR 2.81, 95%-CI 1.03-7.64, p=0.042).CONCLUSION: The CTLA4 -318/C/T SNP was associated with an increased risk to develop IgAN, while the CT60 G/A genotype significantly associated with the risk for higher proteinuria suggesting a possible role for CTLA-4 in IgAN.
KW - CTLA-4 Antigen
KW - Case-Control Studies
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Glomerulonephritis, IGA
KW - Humans
KW - Polymorphism, Single Nucleotide
KW - Proteinuria
KW - Journal Article
U2 - 10.1159/000488069
DO - 10.1159/000488069
M3 - SCORING: Journal article
C2 - 29539619
VL - 43
SP - 360
EP - 366
JO - KIDNEY BLOOD PRESS R
JF - KIDNEY BLOOD PRESS R
SN - 1420-4096
IS - 2
ER -
