232 Impact of Cytokine Gene Polymorphism on BK Virus Nephropathy in a Large Cohort of Kidney Transplant Recipients

Wednesday, October 24, 2012
Westin Diplomat Resort
Don Vu, PharmD, &, Ph.D1, Prashant Sakharkar, Pharm.D, &, MPH2, Tariq Shah, M.D.3, Robert Naraghi, M.D.3, Ian V. Hutchinson, Ph.D., DSc4 and David I. Min, Pharm.D.5
1National Institute of Transplantation and Western University of Health Sciences, College of Pharmacy, Los Angeles, CA
2Western University Health of Sciences, Pomona, CA
3National Institue of Transplantation and St. Vincent Medical Center, Los Angeles, CA
4USC School of Pharmacy, Los Angeles, CA
5Western University of Health Sciences, College of Pharmacy and National Institute of Transplantation, Los Angeles, CO

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.