A Polymorphism in the Zinc Transporter Gene, SLC30A8, Confers Resistance Against Posttransplantation Diabetes Mellitus in Renal Allograft Recipients

Abstract

Objective: Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients, and insulin secretory defects play an important role in the pathogenesis of PTDM. The R325W (rs13266634) nonsynonymous polymorphism in the islet-specific zinc transporter protein gene, SLC30A8, has been reported to be associated with type 2 diabetes and possibly with a defect in insulin secretion. This study investigated the association between genetic variations in the SLC30A8 and PTDM in renal allograft recipients.

Research Design and Methods: A total of 624 unrelated renal allograft recipients without previously diagnosed diabetes were enrolled. Rs13266634 was genotyped in the cohort, which consisted of 174 PTDM patients and 450 non-PTDM subjects. The genotyping of the SLC30A8 polymorphism was performed using real-time PCR.

Results: The prevalence of PTDM was 33.8% in patients carrying the R/R genotype, 26.8% in patients with the R/W genotype, and 19.8% in patients with the W/W genotype. There was a strong association between the number of W alleles and PTDM risk reduction (p for trend=0.007). Patients with at least one T allele showed a decreased risk of PTDM compared to those with the R/R genotype (R/W; risk ratio=0.78, p=0.126, W/W; risk ratio= 0.52, p=0.007). The effect of the SLC30A8 genotype remained significant after adjustments for age, gender, body weight gain, and type of immunosuppressant (R/W; hazard ratio=0.77, p=0.114, W/W; hazard ratio=0.58, p=0.026).

Conclusions: These data provide evidence that the SLC30A8 rs13266634 gene variation is associated with protection from the development of PTDM in renal allograft recipients.