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

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>Tremained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TThad 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>Twas 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>Twas 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.