engleski

CXCL9 and CXCL10 gene polymorphisms are associated with earlier onset of acute cellular rejection after liver transplantation

Background and Aims: Despite the improvement and optimization of immunosuppressive protocols, acute cellular rejection (ACR) is still a frequent complication after liver transplantation. Recent studies showed that increased concentrations of chemokines CXCL9 and CXCL10 are associated with the ACR occurrence. The aim of this study was to examine the association of CXCL9 and CXCL10 single nucleotide polymorphisms with ACR after liver transplantation. Method: DNA was isolated from the whole blood of 215 patients transplanted due to alcoholic liver disease from 1/2009 to 3/2017 in University Hospital “Merkur”, Zagreb, Croatia. Polymorphisms of CXCL9 (rs10336) and CXCL10 (rs3921) were determined by polymerase chain reaction using commercially available TaqMan SNP assays. ACR was defined as biopsy proven (Banff score ≥3) within 6 months after liver transplantation. All patients received the same immunosuppressive protocol comprising of calcineurin inhibitors, steroids (discontinued after 3 months) and mycophenolate mofetil. Results: 59 patients with ACR and 156 patients without ACR were included into the study. There were no statistically significant differences in age, sex or MELD score at the time of transplant between rejection and non-rejection groups. Genotypes were in Hardy-Weinberg equilibrium (p > 0.05), with strong linkage disequilibrium (D’ = 0.99, r = 0986) between CXCL9 and CXCL10. In the rejection group 22 (37.3%) patients had GG, 25 (42.4%) had AG and 12 (20.3%) had AA genotype of the CXCL9 polymorphism, with similar genotype distribution observed in the non-rejection group, in which 54 (34.6%) patients had GG, 75 (48.1%) had AG and 27 (17.3%) had AA genotype. Lack of association between CXCL9 genotypes and incidence of ACR was found in codominant, dominant, recessive, overdominant or log- additive model (p > 0.05). Similar results were obtained for CXCL10 genotypes. On the other hand, we observed significant association between both CXCL9 and CXCL10 genotypes and the time of ACR occurrence. Patients with CXCL9 genotype AA developed ACR earlier (median 5 days (IQR 4.0–7.5)) than patients with the GG genotype (median 8 days (IQR 6.0–18.3)) (p = 0.003), with similar results for CXCL10 gene (CC vs GG ; p = 0.005). Conclusion: Single nucleotide polymorphisms of CXCL9 (rs10336) and CXCL10 (rs3921) are not associated with the incidence of acute cellular rejection after liver transplantation, but are associated with the time of ACR onset.

chemokines ; acute cellular rejection ; liver transplant

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