Genetic polymorphisms in MHC-encoded antigen processing gene TAP2: a case-control study in end-stage renal disease patients of North India.

摘要

AIM: TAP2 genes are involved in antigen presentation by MHC class I molecules, especially in the transport of endogenous peptides. As for most MHC genes, a polymorphism has been described and the possibility that it could influence the recipient immune response by modulating antigen presentation in renal disorders. The aim of our study was to analyze TAP2 gene polymorphism in between ESRD (end stage renal disease) patients and healthy controls in our North Indian population. MATERIALS AND METHOD: We analyzed 3 polymorphisms in the TAP2 gene viz. 565 (G-->A, Ala-->Thr), 379 (G-->A, Val-->Ile) and 665 (A-->G, Thr-->Ala), by amplification refractory mutation system-polymerase chain reaction, (ARMS-PCR) methodology using SPSS 11.0 (Chicago, IL, U.S.A.) in a hospital based case-control study in 148 ESRD cases and 230 healthy controls. They were age and sex matched and were of similar ethnicity. RESULTS: Our results showed that only TAP2 G>A 379 Val/Ile was found to be significant for end stage renal disease patients. Furthermore, 2 haplotypes, Ile(379)-Thr(665) and Ile(379)-Ala(665) (p=0.001; OR=0.28 and p=0.030; OR=4.30 respectively) were also associated with the disease and on the other hand gene combination effect revealed protective pattern with ESRD (Val/Ile(379)-Thr/Thr(665) p=0.007; OR=0.30). These results suggested that the currently described polymorphism in the limited coding region of TAP2 genes individually does not influence end stage renal disease risk. It however, proposes a strong link when in combination with each other. CONCLUSION: The study suggests that the possibility exists that some alleles, in the TAP genes, might confer susceptibility or protection in patients with ESRD which might prove to be helpful in identifying individuals at a higher risk for progressive renal insufficiency.