Association of genetic polymorphisms of interleukins with new-onset diabetes after transplantation in renal transplantation.

BACKGROUND

New-onset diabetes after transplantation (NODAT) is a serious metabolic complication. Although β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis has not been identified. Although several cytokines have been suggested to be involved in the inflammation of islet beta cells in diabetes mellitus, only rarely have studies examined β-cell dysfunction in NODAT. Therefore, we examined the association between NODAT and 18 single nucleotide polymorphisms (SNPs) located within the 10 genes of interleukins (IL) or their receptors, which might be related with β-cell dysfunction after kidney transplantation.

METHODS

A total of 306 renal transplants recipients were included without a history of diabetes. We analyzed the association between NODAT development and a panel of 18 SNPs within 10 genes of IL or their receptors.

RESULTS

In terms of allele frequencies, rs2069763T (IL-2), rs1494558A and rs2172749C (IL-7R), and rs4819554A (IL-17R) were significantly higher in patients with NODAT. Eleven SNPs among 18 (61.1%) were significantly associated with NODAT development after adjusting for age, sex, and tacrolimus usage. They include IL-1B (rs3136558), IL-2 (rs2069762), IL-4 (rs2243250, rs2070874), IL-7R (rs1494558, rs2172749), IL-17RE (rs1124053), IL-17R (rs2229151, rs4819554), and IL-17RB (rs1043261, rs1025689).

CONCLUSIONS

The data suggest that inflammation of islet β cells might play a crucial role in the pathogenesis of NODAT in renal transplantation recipients. In particular, significant variations of IL-7R, IL-17E, IL-17R, and IL-17RB, which was recently reported to be associated with type 1 diabetes mellitus, could be associated with the pathogenesis of NODAT in renal transplant recipients.