A study of the impact of cytokine gene polymorphism in acute rejection of renal transplant recipients

Abstract

Acute rejection is a common phenomenon in transplantation. Inflammatory and anti-inflammatory mediators affect the graft microenvironment. Th1 responses cause acute rejection while Th2 immune responses help the survival of the graft. In this study, we evaluated gene polymorphisms of IL-6 G-174C, TGF-β T+869C, IL-4 C-590T, and IFN-γ T+874A cytokines in renal transplant patients. ARMS-PCR method was used to characterize IL-6 G-174C (rs76144090), TGF-β T+869C (rs1800471), and IFN-γ T+874A (rs2430561) polymorphisms and PCR-RFLP, for characterization of IL-4 C-590T (rs2243250) in 100 renal transplant patients. Acute rejection episodes were diagnosed according to the standard criteria. Analysis of the results showed that IL-6-174 GG genotype (P=0.018, OR=3.023, 95% CI=1.183-7.726) and IL-6-174G allele (P=0.046, OR=2.114, 95% CI=1.005-4.447) were more frequent, but IL-6-174GC genotype was less frequent in acute rejection of kidney transplantation in comparison with control group (P=0.024, OR=0.302, 95% CI=0.103-0.883). IFN-γ+874 T allele was associated with a higher risk of acute rejection (P=0.019, OR=2.088, 95% CI=1.124-3.880) while IFN-γ+874 AA genotype was associated with a lower risk of rejection (P=0.023, OR=0.318, 95% CI=0.115-0.875). Frequencies of TGF-β T+869C and IL-4 C-590T were not significantly different (P>0.05). Consequently, our results show that IL-6 G-174C and IFN-γ T+874A gene polymorphisms have predictive values for acute rejection after renal transplantation in Iranian patients.

Association of genetic variation in co-stimulatory molecule genes with outcome of liver transplant in Iranian patients

“…Although no significant differences were observed between CTLA4 318 and CD28, significant differences between CTLA4 49 and liver transplant outcomes were detected (Marder et al, 2003b). In a previous study, we reported that there is a significant association between IFN-γ, IL-6 polymorphism liver, and kidney transplant outcome (Karimi et al, 2011(Karimi et al, , 2012.…”

Association of interleukin4 gene polymorphisms of recipients and donors with acute rejection following living donor liver transplantation

“…Several studies have investigated the risk of recipient IL4 polymorphisms on acute rejection of allografts in kidney or heart transplantation [1,[8][9][10][16][17][18]. The TT genotype of IL4-33 is reported to be associated with high production of IL-4 [4,15]. Nevertheless, it is difficult to speculate how genetic polymorphisms of IL4-33 might influence the development of rejection.…”

“…Cytokine genotypes have been previously studied in patients who have undergone solid organ transplantation, and certain polymorphisms have been found to affect the development in graft rejection [1][2][3][4][5][6][7][8][9][10]. In the field of organ transplantation, pro-inflammatory Th1 cytokines are believed to be involved in acute transplant rejection, by directly contributing to graft damage.…”

Frequency of TGF-βand IFN-γGenotype as Risk Factors for Acute Kidney Injury and Death in Intensive Care Unit Patients

“…In contrast, Karimi et al reported an association between the TT homozygote for IFN- γ (high producer) and acute rejection renal transplantation [29]. These authors suggest that these conditions are associated with renal injury and may contribute to evolution for AKI [7, 9].…”