Polymorphism of the vitamin D receptor and risk of new-onset diabetes after transplantation in hispanic kidney transplant recipients

Abstract

Background: New-onset diabetes after transplantation (NODAT) is an important metabolic complication that increases risk of cardiovascular disease and is associated with lower allograft and patient survival in renal transplant recipients (RTRs). Polymorphism of vitamin D receptor (VDR) gene has been widely explored due to the complex role played by vitamin D in renal transplant outcomes. We investigated whether VDR gene polymorphism, Taq1 A/G located in exon 9 associated with the development of NODAT in Hispanic RTRs.Methods: We assessed 129 RTRs with no evidence of pre-existing diabetes who developed NODAT and 186 controls with no history of diabetes. NODAT was defined as fasting glucose levels ≥126mg/dL on two or more occasions or taking any insulin or oral hypoglycemic agents for a month or later after kidney transplantation. The Taq1 A/G (rs731236) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Cumulative incidences of NODAT were estimated by the Kaplan-Meier product-limit method and graft survival by Log rank (Mantel Cox). Cox regression analysis was used to examine for NODAT-associated non-genetic and genetic factors.Results: The genotype frequency of the Taq1 A/G polymorphism differed significantly between NODAT patients and controls (p=0.02). The Taq1 A allele (AA+AG) genotype remained significant on regression analysis (OR=3.31, CI=1.09-10.0, p=0.034). Among the clinical factors sirolimus and acute rejection remained significant whereas age showed borderline significance on regression analysis. Renal function at 1 year, as assessed by serum creatinine levels, was poorer in NODAT patients compared with control (1.6 ± 1.4 mg/dL vs. 1.25 ± 0.9 mg/dL, p=0.007). Kaplan-Meier survival analysis also suggested more than 1.9 fold increased risk of allograft failure in NODAT patients (Log rank p=0.018). After 3 years, graft survival began to decrease in the NODAT group compared with control group.Conclusion: Study results indicate that the Taq1 polymorphism of VDR is significantly associated with NODAT.