Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients. Issue 1 (13th July 2018)

• Record Type: Journal Article
• Authors: 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‐Francois; Soccal, Paola M.; Kutalik, Zoltan; Marques‐Vidal, Pedro; Vollenweider, Peter; Recher, Mike; Hess, Christoph; Pascual, Manuel; Eap, Chin B.
• Is Part Of: American journal of transplantation. Volume 19:Issue 1(2019)
• Page Start: 238
• Page End: 246
• Publication Date: 2018-07-13
• Subjects: clinical research/practice -- diabetes -- genetics -- new onset/posttransplant; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.14971
• Languages: English
• ISSNs: 1600-6135

Abstract

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 r s2114592‐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. Abstract : A genetic polymorphism in SP110, an immune‐ and inflammation‐related gene, is associated with new‐onset diabetes posttransplantation in a cohort of solid organ transplantation recipients, with carriers of the rs2114592‐TT genotype having nearly a 10 times increased risk of diabetes.