Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients

Am J Transplant. 2019 Jan;19(1):238-246. doi: 10.1111/ajt.14971. Epub 2018 Jul 13.

Abstract

New-onset diabetes mellitus after transplantation (NODAT) is a complication following solid organ transplantation (SOT) and may be related to immune or inflammatory responses. We investigated whether single nucleotide polymorphisms (SNPs) within 158 immune- or inflammation-related genes contribute to NODAT in SOT recipients. The association between 263 SNPs and NODAT was investigated in a discovery sample of SOT recipients from the Swiss Transplant Cohort Study (STCS, n1 = 696). Positive results were tested in a first STCS replication sample (n2 = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n3 = 156). Associations with diabetic traits were further tested in several large general population-based samples (n > 480 000). Only SP110 rs2114592C>T remained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TT had 9.9 times (95% confidence interval [CI]: 3.22-30.5, P = .00006) higher risk for NODAT in the combined STCS samples (n = 1184). rs2114592C>T was further associated with NODAT in the second SOT sample (odds ratio: 4.8, 95% CI: 1.55-14.6, P = .006). On the other hand, SP110 rs2114592C>T was not associated with diabetic traits in population-based samples, suggesting a specific gene-environment interaction, possibly due to the use of specific medications (ie, immunosuppressants) in transplant patients and/or to the illness that may unmask the gene effect.

Keywords: clinical research/practice; diabetes; genetics; new onset/posttransplant.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Diabetes Mellitus / etiology*
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / immunology
  • Female
  • Gene-Environment Interaction
  • Heterozygote
  • Homozygote
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Inflammation / genetics*
  • Inflammation / immunology
  • Male
  • Middle Aged
  • Odds Ratio
  • Organ Transplantation*
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Switzerland / epidemiology
  • Transplant Recipients*
  • Young Adult

Substances

  • Immunosuppressive Agents

Grants and funding