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Association between a polymorphism in the IL-12p40 gene and cytomegalovirus reactivation after kidney transplantation
Authors:Hoffmann Thomas W  Halimi Jean-Michel  Büchler Mathias  Velge-Roussel Florence  Goudeau Alain  Al Najjar Azmi  Boulanger Marie-Denise  Houssaini Tarik Sqalli  Marliere Jean-Frédéric  Lebranchu Yvon  Baron Christophe
Institution:JE2448 Cellules Dendritiques et Greffes, UFR de Médecine, Université Fran?ois Rabelais, Tours, France.
Abstract:BACKGROUND: Cytomegalovirus (CMV) infection is associated with a significant rate of morbidity after organ transplantation. The genetic factors influencing its occurrence have been little investigated. IL-12 plays a crucial role in anti-infectious immune responses, especially by stimulating IFNgamma production. An A-to-C single nucleotide polymorphism (SNP) within the 3'-untranslated region of the IL-12p40 gene has been characterized and was reported to be both functionally and clinically relevant. However, the impact of this single nucleotide polymorphism on events after organ transplantation has never been reported. METHODS: In this study, we investigated the impact of the 3'-untranslated region polymorphism on the occurrence of CMV infection in 469 kidney recipients transplanted at the University Hospital of Tours between 1995 and 2005. The polymorphism was genotyped using the restriction fragment length polymorphism method and CMV infection was determined by pp65 antigenemia. RESULTS: Multifactorial Cox regression analysis demonstrated that the presence of the C allele was an independent risk factor for CMV infection (OR=1.52, P=0.043), the risk being even higher when study was restricted to patients with positive CMV serological status before the graft and who did not receive any CMV prophylaxis (OR=1.88, P=0.028). CONCLUSIONS: This study identified a new genetic risk factor for CMV reactivation after kidney transplantation. The results of our study suggest that C carriers might especially benefit from CMV prophylaxis.
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