The influence of CTLA-4 gene polymorphism on long-term kidney allograft function in Caucasian recipients.
The aim of the study was to examine whether CTLA-4 (CD152) and CD28 gene polymorphisms affect the outcome of kidney transplantation (KTx). Polymorphisms of the CTLA-4 gene (-318 C>T, +49 A>G, and the microsatellite polymorphism in the 3'UTR of exon 4 (AT)(n)) and a CD28 gene (IVS3 +17T>C) were investigated in 314 allograft recipients with a mean age of 41.9+/-12 years. The median time since KTx was 97.5 months. The genotypes of the SNPs were determined by SSP-PCR and (AT)(n) genotype by PCR and capillary electrophoresis (ABI Prism 310). In general, no relationship was found between the allele variants and acute rejection or graft function. Univariate and multivariate analyses showed no influence of CTLA-4 or CD28 polymorphism on graft/patient survival. In the individuals bearing the combination of the homozygous variant of low AT repeat number (82 bp) and the homozygous variant A (adenine) in CTLA-4 +49 A>G, higher eGFR was observed at one year after KTx, which was also maintained at 10 years. In summary, 24.2% of the studied patients carrying the "favorable" CTLA-4 genotype exhibited significantly higher allograft function than the 16.9% recipients with the "unfavorable" genotype up to 10 years post transplantation.
Kusztal
Mariusz
M
Department of Nephrology and Transplantation Medicine, Medical University of Wrocław, Traugutta 57, 50-417 Wroclaw, Poland. mariok@tlen.pl
Kościelska-Kasprzak
Katarzyna
K
Drulis-Fajdasz
Dominika
D
Magott-Procelewska
Maria
M
Patrzałek
Dariusz
D
Janczak
Dariusz
D
Chudoba
Paweł
P
Klinger
Marian
M
D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D005838:Genotype; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044465:White People
D015703:Antigens, CD; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human