A polymorphism in the zinc transporter gene SLC30A8 confers resistance against posttransplantation diabetes mellitus in renal allograft recipients

Diabetes. 2008 Apr;57(4):1043-7. doi: 10.2337/db07-0761. Epub 2007 Dec 27.

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 gene 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 posttransplantation diabetic patients and 450 non-posttransplantation diabetic 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 with those with the R/R genotype (R/W, risk ratio [RR] 0.78, P = 0.126; W/W, RR 0.52, P = 0.007). The effect of the SLC30A8 genotype remained significant after adjustments for age, sex, body weight gain, and type of immunosuppressant (R/W, hazard ratio [HR] 0.77, P = 0.114; W/W, HR 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cation Transport Proteins / genetics*
  • DNA / blood
  • DNA / genetics
  • DNA / isolation & purification
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / prevention & control*
  • Gene Frequency
  • Genetic Variation
  • Genotype
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Kidney Transplantation / physiology*
  • Patient Selection
  • Polymorphism, Genetic*
  • Postoperative Complications / prevention & control
  • Retrospective Studies
  • Risk Reduction Behavior
  • Transplantation, Homologous
  • Zinc Transporter 8

Substances

  • Cation Transport Proteins
  • Hypoglycemic Agents
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • DNA