Purpose: BK virus nephropathy (BKVN) has emerged as an important cause of progressive graft dysfunction in renal transplantation, with incidence rates ranging from 1 to 10%. Several single nucleotide polymorphisms in the promoter of cytokines have been associated with parvovirus B19, hepatitis C virus, HIV-1/AIDS infection. Deregulated production of pro-or anti-inflammatory cytokines plays an important role in the disease progression. We studied the association of gene polymorphisms in the interleukin-10 gene (IL10; 1082 A>G, -592 A>C), interferon-gamma gene (IFNG; +874 A>T), and tumor necrosis factor-alpha gene (TNFA; -308 A>G) with BKVN, taking into account the role that these cytokines might play in the immune response against BK virus.
Methods: The IL10, IFNG and TNFA genotypes were determined in 70 kidney allograft recipients with BKVN and 182 without BKVN. Distributions of genotypes were compared to the Hardy-Weinberg theoretical distribution using chi-square test. Nongenetic and genetic characteristics were included in the multivariate risk model. A p value less than 0.05 was considered statistically significant.
Results: BKVN developed at an average of 1.2 years post-transplantation (range from 38 days to 5 years). Analysis of the results showed that IFNG +874 A>T A allele (p=0.019, OR=1.76) and IL 10 (-592 A/C) AC genotype (p=0.004, OR = 2.4) were significantly associated with BKVN. On the other hand, IFNG 874 A>T AA and IL10 (-592 A/C) CC were protective (OR 0.11 and 0.41, respectively; both p<0.05). The allelic as well as genotypic frequencies of TNFA (-308G >A) and IL10 (-1082 A>G) gene polymorphism did not significantly differ between BKVN and without BKVN group. Of the nongenetic factors, use of tacrolimus and older age were associated with increased risk for BKVN.
Conclusion: The results suggest that IFNG (+874 A>T) and IL10 (-592 A/C) gene polymorphisms have predictive values for the development of BKVN in renal allograft recipients.