The Role of an iNOS Polymorphism at the Post-Diagnosis Diabetes Development in Children with Type 1 Diabetes

Johannesen J, Eriksen V, Andersen MLM, Nielsen LB,

Objective: A missense polymorphism (rs2297518) of the inducible nitric oxide synthase (iNOS) gene causing a serine to leucine substitution at amino acic position 608 has previously been associated to the development of type 1 diabetes (T1DM). Activation of iNOS is a main effector pathway in cytokine mediated beta-cell destruction. Here, we evaluate whether rs2297518 associates to interleukin-1β (IL-1β) levels, metabolic control and development of autoantibodies 12 months post-diagnosis. Materials and Methods: The International Hvidoere cohort includes 275 children from 18 paediatric centers. The rs2297518 was tested in 256 participants and analyzed for its association to serum IL-1β levels, concentration of autoantibodies and residual beta-cell function as assessed by stimulated C-peptide, HbA1c and calculated insulin dose adjusted HbA1c (IDAA1c) at 1, 6 and 12 months post-diagnosis. Results: At 1 month IL-1β was detected more frequently in CC-genotype individuals as compared to CT and TT individuals, 24/168 vs. 3/75 and 0/9, respectively (p=0.03). This effect was not present at 6 and 12 months post-diagnosis. The iNOS polymorphism was not associated to diabetic ketoacidosis status at diagnosis, stimulated C-peptide, measured HbA1c levels or the calculated IDAA1c at any time point during the first 12 months post-diagnosis. Conclusion: The rs2297518 polymorphism of the iNOS gene may be involved in circulating IL-1β levels after diagnosis. However, this polymorphism does not seem to influence the metabolic outcome the first 12 months after diagnosis.

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