The minor allele frequencies for the G-allele (rs187238; IL-18) in healthy and T1D groups were 28.5% [95%CI = 23-34%] vs 31.6% [95%CI = 26-37%], P = 0.416, and for the T-allele (rs5435, GLUT4) were 33% [95%CI = 28-39] vs 27% [95%CI = 23-33%], P = 0.167, respectively.
Additionally, correlation studies also revealed that IL-18 and IL-18BP are positively correlated with HbA1c levels in T1D patients, suggesting a potential link between IL-18 and metabolic control in these patients.
Therefore, we examined the significance of IL-18-137G/C, IL-18-607C/A, and IL-12B A/C polymorphisms in Croatians (187 patients, 236 controls), not only as factors that contribute to susceptibility to T1DM, but also as determinants of the clinical presentation of disease.
The allelic and genotypic frequencies of the IL-18 and IL-12p40 polymorphisms did not differ significantly between subjects with T1DM and the controls (p>0.05).
High levels of IL-18 in patients with type 1 DM is related to short and long term glycemic control and HDL-C levels but not to microvascular complications.
Statistically significant difference was found in the distribution of IL-18 promoter -607 (C/A) polymorphism between LADA and T1DM in adults (P < 0.01).
Our results suggest that NeuroD1 exon 2 and IL-18 promoter gene polymorphisms are not associated with development of T1DM susceptibility in the population of South Croatia.
Non-MHC genes associated with susceptibility to type 1 diabetes in both Japanese and Caucasoid patients include polymorphisms in the insulin gene, the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, the interleukin-18 (IL18) gene and the major histocompatibility complex class I chain-related gene A (MICA) gene.
The results of this study show that polymorphisms of IL-18 promoter confer susceptibility to Type 1 diabetes in Iranian individuals with onset at older ages.
We conclude that common allelic variation in IL18 is unlikely to contribute substantially to type 1 diabetes susceptibility in the populations tested and recommend routine application of tests for HWE in population-based studies for genetic association.
Since in previous studies IL-18 and sICAM-1 were found to be predictors of death in subjects with CHD, one could speculate that high levels of IL-18 observed in subjects with genetic predisposition, but still with normal glucose levels, are an in addition to hyperglycaemia, pathogenic factors responsible for a higher risk of acute coronary events in subjects with diabetes type 1.
These results suggest that the IL-18 gene promoter polymorphisms are not associated with adult type 1 diabetes or LADA susceptibility, and according to our findings genes involved in onset and progression of LADA and T1DM are probably different.
In conclusion, our data do not support the strong positive associations of IL18 promoter polymorphisms with type I diabetes reported in previous smaller studies.
These results suggest that the IL-18 gene polymorphism is associated with a type 1 diabetes susceptibility, and there might be a gene-gene interaction between IL-18 gene with susceptible CTLA-4 gene.
These results suggest that polymorphisms of the IL-18 gene are not associated with a susceptibility to AITD and type 1 diabetes coexistent with AITD in Japanese population.
Because increased production of IFN-gamma could be secondary to a dysregulated synthesis of IL-18, we compared the circulating levels of IL-18 in patients with newly diagnosed Type I diabetes with those of non-diabetic first-degree relatives and healthy control subjects.