Abstract
Objective: Post transplantation diabetes mellitus (PTDM) is a major complication associated with kidney transplantation due to the immunosuppressive therapy. Defects in insulin secretion play a pivotal role in the pathogenesis of PTDM and zinc also playsan important role in all process of insulin trafficking, i. e. synthesis, storage and secretion. Gene polymorphisms in the transcription factor 7-like 2 (TCF7L2) and zinc transporter protein member 8(SLC30A8) was reported to be associated with type 2 diabetes, possibly associated with an insulin secretion defect. The aim of this study was to investigate the association between genetic variations in TCF7L2, SLC30A8 and PTDM in renal allograft recipients.
Method: PCR and RFLP based genotyping of TCF7L2 (rs# 7903146) and SLC30A8 (rs# 13266634) polymorphisms were carried out in 364 individuals which included patients who had undergone renal transplant (n= 140), 42 of which developed post-transplant diabetes mellitus and healthy control volunteers (n= 224). DNA was isolated from peripheral blood and TCF7L2 and SLC30A8 gene analysis was carried out for genotypes and alleles.
Results: In the present study the genotype distribution of TCF7L2 TT genotype (26.1%) was high in cases when compare to Controls (8.2%) and the incidence of PTDM was significantly higher in patients with T allele and TT genotype (OR 2.315, 95% CI= 1.466-3.656, p= 0.0003 and OR 2.403, 95%, CI= 1.212-4.766, p= 0.01) respectively. Whereas SLC30A8 TT genotype (14.2%) distribution was also higher in patients when compared to controls (4.2%), PTDM incidence also showed significant association with T allele and TT (OR 3.057, 95%, CI= 1.89-4.941, p< 0.0001 and OR= 3.929, 95%, CI= 2.085-7.612, p< 0.0001).
Discussion: TCF7L2 and SLC30A8 polymorphisms could be used as biomarkers to identify individuals at high risk of developing PTDM, it would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals undergoing transplant. Present study shows that importance of these polymorphisms in increasing the risk of PTDM in patients with ESRD belonging to the Asian Indian population.