Association of genetic variation in inducible costimulator gene with outcome of kidney transplantation.
BACKGROUND
The closely-linked genes of CD28, cytotoxic T-lymphocyte associated antigen 4 (CTLA4), inducible costimulator (ICOS), and programmed cell death 1 on chromosome 2q encode costimulatory molecules, which are regulators of the T-cell activity. The T-cell mediated immune response has a major role in allograft rejection. Hence, the variation in these genes may have an effect on graft survival and the amount of immunosuppression needed, but so far the studies have restricted solely to the CTLA4 gene.


METHODS
We determined 13 single nucleotide polymorphisms in CD28, CTLA4, ICOS, and PPCD1 genes in 678 adult patients who received a kidney from deceased donor. The effect of genetic variation on the outcome of renal transplantation was analyzed.


RESULTS
Two markers on the ICOS gene, rs10183087 and rs4404254, were associated with delayed graft function (odds ratio=5.8; P=0.020 and odds ratio=5.8; P=0.019, respectively). Interestingly, the same ICOS variation has been shown to regulate the expression level of ICOS. We also demonstrated an association of the ICOS polymorphism rs10932037 with the graft survival (P=0.026).


CONCLUSIONS
The present results indicate that potentially functional genetic variation in T-cell costimulatory molecule ICOS has an effect on the outcome of kidney transplantation.
Haimila
Katri
K
Research and Development, Finnish Red Cross Blood Service, Helsinki, Finland. katri.haimila@bts.redcross.fi
Turpeinen
Hannu
H
Alakulppi
Noora S
NS
Kyllönen
Lauri E
LE
Salmela
Kaija T
KT
Partanen
Jukka
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D018106:CD28 Antigens / Q000235:genetics; D060908:CTLA-4 Antigen; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D006084:Graft Rejection / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D061027:Programmed Cell Death 1 Ligand 2 Protein; D016896:Treatment Outcome; D055815:Young Adult
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers; D006680:HLA Antigens; C556692:ICOS protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D036341:Intercellular Signaling Peptides and Proteins; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein