Matrix Metalloproteinase Gene Polymorphisms and New-Onset Diabetes After Kidney Transplantation in Korean Renal Transplant Subjects.

ABSTRACT

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious metabolic complication that may follow renal transplantation. Matrix metalloproteinases (MMPs) contribute to insulin insufficiency and beta-cell dysfunction in a rat model. The MMP-2 concentrations were lower in patients with type 2 diabetes mellitus, and the plasma MMPs levels were related to diabetes. Similar to the pathogenesis of type 2 diabetes mellitus, insulin resistance and insulin secretion dysfunction occur in patients with the development of NODAT. Therefore, we examined the association between NODAT and 11 single-nucleotide polymorphisms (SNPs) located within the 3 genes of MMPs that might be related to NODAT. METHODS: A total of 309 renal transplant recipients without a history of diabetes were included in this study. DNA was extracted from the blood samples of recipients, and we analyzed the association between the development of NODAT and a panel of 11 SNPs within 3 MMP genes (MMP-1, MMP-2, and MMP-3). RESULTS: In terms of allele frequencies, rs243849*C (MMP-2) was significantly higher in patients with NODAT. Two of the 11 (18.1%) SNPs were significantly associated with NODAT development after adjusting for age, sex, and tacrolimus usage MMP-2 (rs1132896) and MMP-2 (rs243849). In the multiple logistic regression analysis, these 2 SNPs were significantly associated with the development of NODAT in the codominant and recessive or codominant and dominant models. CONCLUSIONS: MMP-2 gene rs1132896 and rs243849 polymorphisms may serve as genetic markers for the development of NODAT. The exact molecular mechanisms still must be clarified.