Association of vitamin D binding protein polymorphism with long-term kidney allograft survival in Hispanic kidney transplant recipients Don Vu • Prashant Sakharkar • Eglis Tellez-Corrales • Tariq Shah • Ian Hutchinson • David I. Min Received: 11 July 2012 / Accepted: 3 October 2012 / Published online: 17 October 2012 Ó Springer Science+Business Media Dordrecht 2012 Abstract Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investi- gated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant popu- lation. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide poly- morphisms of VDR: FokI C [ T (rs2228570), BsmI G [ A (rs1544410), ApaI T [ G (rs7975232), and TaqI T [ C (rs731236). We also performed genotyping for one com- mon polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homo- zygous GG for the rs4588 G [ T allele in the VDBP gene (GG vs. GT ? TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG ? TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C [ T, BsmI G [ A, ApaI T [ G, and TaqI T [ C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP G [ T polymorphism (rs4588) and two haplotypes (GTCG and ACCA) of VDR appear to be associated with renal allograft outcomes among Hispanic allograft recipients. Keywords VDR Á VDBP Á Gene polymorphisms Á Rejection Á Survival Á Hispanics Introduction Kidney transplantation is the treatment of choice for patients with end-stage renal failure, offering both improved survival and quality of life [1]. Long-term graft survival is negatively impacted by acute rejection (AR) episodes after transplan- tation, as these are the major predictor for chronic rejection, which is responsible for most of allograft dysfunction after the first few years post-transplant. Vitamin D plays a significant role in most metabolic pathways, such as those involved in the immune response and cancer [2]. 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, binds to intracellular vitamin D receptors (VDR) that then function as transcription factors to regulate gene expression [3]. Vitamin D3 is known to inhibit T cell activation and secretion of different cytokines such as interleukin-1 (IL-1), IL-2, IL-6, IL-12, tumor necrosis D. Vu Á I. Hutchinson Mendez National Institute of Transplantation, Los Angeles, CA, USA D. Vu Á T. Shah Á D. I. Min Saint Vincent Medical Center, Los Angeles, CA, USA D. Vu Á P. Sakharkar Á T. Shah Á D. I. Min (&) Western University of Health Sciences, 309 E. 2nd Street, Pomona, CA 91766, USA e-mail: dmin@westernu.edu E. Tellez-Corrales Nova Southeastern University, Miami, FL, USA T. Shah Á I. Hutchinson University of Southern California, Los Angeles, CA, USA T. Shah Transplant Research Institute, Los Angeles, CA, USA 123 Mol Biol Rep (2013) 40:933–939 DOI 10.1007/s11033-012-2134-6