HLA-G Polymorphism, a Molecule Involved in Materno-Fetal Tolerance Is Associated with a Reduction of Acute Rejection and Improved Graft Survival in Renal Transplantation

L. Quteineh, C. Verstuyft, B. Charpentier, L. Becquemont, A. Durrbach
Pharmacogenetic, Hospital, Le Kremlin Bicetre, France; Nephrology, IFRNT, Hospital, Le Kremlin Bicetre, France; U1014, INSERM, Villejuif, France
Abstract number: 356

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Introduction: Few markers of good outcome of kidney transplants have been demonstrated. We have shown that HLA-G, a protein belonging to the non-classical class I molecules and involved in feta-maternal tolerance is associated with a good outcome of combined liver and kidney transplants. It is associated with a reduced risk of liver and kidney rejection. HLA-G is also associated with a reduced risk of cardiac rejection. In kidney transplantation, the group P. Terazaki showed that soluble HLA-G is associated with a reduction of number and titer of anti-HLA antibodies. Several polymorphisms (SNPs) of HLA-G have been described. The purpose of this study is to determine whether certain HLA-G polymorphisms are associated with a better outcome of renal transplantation.

Materials and Methods: 300 patients of the TRANSGENE study (declared to the CNIL in 2004) were included. Their genomic DNA was obtained and genotyped for the following SNPs were performed using TaqMan allelic discrimination assay (ABI prism 7000, applied biosystems, Courtaboeuf, France): HLA -725 C> G (rs), HLA 3142 G> C (rs1063320) and deletion / insertion 14 bp. IL10 polymorphism previously described by the group G. Opelz being associated with a good evolution of second transplant was performed: SNP IL10-592C> A (rs1800872) and IL10 -1082 A> G (rs1800896).

Results: In the Caucasian population, the occurrence of acute rejection (RA) was higher in carriers of the -14bp allele vs those with +14bp allele (42% vs 32%, p = 0.02), those with HLA 3142C vs 3142G (43% vs 34%, p = 0.04), or HLA-725G vs HLA-725C (51% vs 37%, respectively p = 0.07). No association was found for IL10 polymorphism. Only the -725 C allele HLA is associated with better graft survival (HR: 0.30, 95% CI: 0.13 to 0.69, P = 0.005).

Conclusion: In our Caucasian population, polymorphisms of HLA-G (-725C, 3142C, and Ins / del 14 bp) are associated with a lower incidence of RA and polymorphism-725C has a better outcome of the renal transplantation.

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