Objective-

Renal Transplantation (RT) is the optimal choice for

end stage renal disease. Despite all advances in the development of

effective immunosuppressive regimens in renal transplantation one of the recent and major problem in renal transplantation is

appearance of de nove DSA (dnDSA) [donor specific anti-human leukocyte antigen

(HLA) antibodies] which is one of the leading cause of allograft loss. Vitamin

D receptor (VDR) is a member of nuclear receptor family which is well

distributed in many cells including immune cells. It acts as a transcription

factor differently in different cells. Polymorphism in VDR gene may be

associated with allograft outcome which has not been studied so far. Therefore,

we speculated the association of VDR gene and incidence of dnDSA after RT.

Method-

58 patients were enrolled in our study who underwent

primary renal transplantation. VDR SNPs FokI [C/T], BsmI [G/A], ApaI [T/G],

TaqI [T/C] polymorphisms were determined by performing PCR-RFLP (Restriction

Fragment Length Polymorphism) method following extraction of genomic DNA from

peripheral blood mononuclear cell of the recipients. These polymorphism were

analyzed with respect to dnDSA and other clinical outcomes. dnDSA was defined as HLA-A, B, Cw, DR or DQ

antibodies directed against the donor HLA that were not present pre-transplant.

MFI values over 1000 were determined to be positive.

Result-

We found that VDR SNP FokI [C/T] was statically significant

(P=0.030*) with incidence of dnDSA i.e. 10 patient out of 47 C

carrier (21.28%) had dnDSA while out of 11 patients none of TT homozygous (0%)

had dnDSA. When we stratified the genotype in three groups we found that CT

heterozygous (4 of 23, 17.39%) and CC homozygous (6 of 24, 25%) had higher

incidence of dnDSA with respect to TT homozygous (0 of 11, 0%) with (P=0.071).

There was no association of other three VDR SNP BsmI, ApaI and TaqI with

incidence of dnDSA or any other clinical outcome post renal transplantation.

Conclusion-

Polymorphism in FokI [C/T] SNP site of VDR gene has

significant association with the incidence of dnDSA after RT. Therefore,

patients who are FokI C carrier of VDR gene may be at higher risk of developing

dnDSA after RT than TT homozygous. This SNP can be used as special predicting

marker to identify the high risk group forehand and better treat them.

CITATION INFORMATION: Das L, Ide K, Tanaka Y, Tanimine N, Verma S, Ohdan H. Significant Association of Vitamin-D Receptor (VDR) Gene Polymorphism and Incidence of De Novo DSA in Renal Transplantation. Am J Transplant. 2016;16 (suppl 3).

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