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

Quteineh, Lina; Wójtowicz, Agnieszka; Bochud, Pierre-Yves; Crettol, Severine; Vandenberghe, Frederik; Venetz, Jean-Pierre; Manuel, Oriol; Golshayan, Dela; Lehmann, Roger; Mueller, Nicolas J; Binet, Isabelle; van Delden, Christian; Steiger, Jürg; Mohacsi, Paul; Dufour, Jean-François; Soccal, Paola M; Kutalik, Zoltan; Marques-Vidal, Pedro; Vollenweider, Peter; Recher, Mike; ... (2019). Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients. American journal of transplantation, 19(1), pp. 238-246. Wiley-Blackwell 10.1111/ajt.14971

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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, n  = 696). Positive results were tested in a first STCS replication sample (n  = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n  = 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.

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