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


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.
Kang
Eun Seok
ES
Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, Korea.
Kim
Myoung Soo
MS
Kim
Yu Seun
YS
Kim
Chul Hoon
CH
Han
Seung Jin
SJ
Chun
Sung Wan
SW
Hur
Kyu Yeon
KY
Nam
Chung Mo
CM
Ahn
Chul Woo
CW
Cha
Bong Soo
BS
Kim
Soon Il
SI
Lee
Hyun Chul
HC
D027682:Cation Transport Proteins / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D003920:Diabetes Mellitus / Q000209:etiology / Q000517:prevention & control*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D018579:Patient Selection; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000517:prevention & control; D012189:Retrospective Studies; D040242:Risk Reduction Behavior; D014184:Transplantation, Homologous; D000075703:Zinc Transporter 8
D027682:Cation Transport Proteins; D007004:Hypoglycemic Agents; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D004247:DNA