S Ong1, S-W Kang2, Y-H Kim1, T-H Kim1, K-H Jeong3, S-K Kim4, Y-C Yoon5, S-K Seo6, J-Y Moon3, S-H Lee3, C-G Ihm3, T-W Lee3, J-H Chung4. 1. Department of Nephrology, College of Medicine, Inje University, Busan, Korea. 2. Department of Nephrology, College of Medicine, Inje University, Busan, Korea. Electronic address: kswnephrology@hotmail.com. 3. Department of Nephrology, College of Medicine, Kyung Hee University, Seoul, Korea. 4. Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Korea. 5. Department of Chest Surgery, College of Medicine, Inje University, Busan, Korea. 6. Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Korea.
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.
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.
Authors: William S Oetting; Baolin Wu; David P Schladt; Weihua Guan; Jessica van Setten; Brendan J Keating; David Iklé; Rory P Remmel; Casey R Dorr; Roslyn B Mannon; Arthur J Matas; Ajay K Israni; Pamala A Jacobson Journal: Transplantation Date: 2019-06 Impact factor: 4.939