Association between a polymorphism in the human programmed death-1 (PD-1) gene and cytomegalovirus infection after kidney transplantation.
BACKGROUND
Cytomegalovirus (CMV) infection is the most frequent infectious disease following organ transplantation. Strategies to prevent this infection remain a matter for debate, and discovering genetic risk factors might assist in adapting preventive strategies. By inhibiting IFNgamma production, programmed death 1 (PD-1) has a crucial role in anti-CMV immune response. A single nucleotide polymorphism (SNP) within intron 4 of the gene (rs11568821), called PD-1.3, has recently been reported to be clinically relevant in several immune disorders. However, its association with CMV infection has never been reported.


METHODS
In this study, the risk of CMV infection according to PD-1.3 genotype was investigated in 469 kidney graft recipients transplanted between 1995 and 2005.


RESULTS
It was found that the A allele was associated with the risk of CMV infection in seropositive patients who did not receive CMV prophylaxis (OR=2.60, p=0.006). Multivariate analysis including other risk factors for CMV infection showed that this allele was independently associated with CMV infection (OR=2.54; p=0.010). Interestingly, combined analysis of PD-1.3 with the IL12B 3'UTR SNPs (previously shown to be associated with CMV infection) revealed that patients with the PD-1.3 A allele had a much higher risk of CMV infection compared to those having neither risk allele (OR=3.76; p=0.0003).


CONCLUSIONS
This study identified a new genetic risk factor for CMV infection after kidney transplantation and suggests that an adjustment of CMV prophylaxis based on genetic markers would merit further investigation.
Hoffmann
Thomas W
TW
Université François Rabelais de Tours, EA 4245 Cellules Dendritiques Immunomodulation et Greffes, UFR de Médecine, Tours, France.
Halimi
Jean-Michel
JM
Büchler
Mathias
M
Velge-Roussel
Florence
F
Goudeau
Alain
A
Al-Najjar
Azmi
A
Marliere
Jean-Frédéric
JF
Lebranchu
Yvon
Y
Baron
Christophe
C
D015703:Antigens, CD / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D003586:Cytomegalovirus Infections / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000209:etiology*; D061026:Programmed Cell Death 1 Receptor
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor