@Article{,
AUTHOR = {Csaba Hermann, Dóra Krikovszky, George Füst, Margit Kovács, Anna Körner, András Szabó, Ádám Vannay, László Madácsy},
TITLE = {Association between interleukin-6 polymorphism and age-at-onset of type 1 diabetes. Epistatic influences of the tumor necrosis factor-α and interleukin-1β polymorphisms},
JOURNAL = {European Cytokine Network},
VOLUME = {16},
YEAR = {2005},
NUMBER = {4},
PAGES = {277--281},
URL = {http://www.techscience.com/ECN/v16n4/66204},
ISSN = {1952-4005},
ABSTRACT = {Multiple immune mediators have been mentioned as playing a role in the pathomechanism of type1
DM. Interleukin (IL)-1β, and tumor necrosis factor (TNF)-α play a central role in the autoimmune destruction of
pancreatic b-cells, whereas IL-6 inhibits TNF-α secretion, and may have some protecting effects. In our study, we
aimed to investigate the association between these three cytokines’ single nucleotide polymorphisms (IL-6 gene
G(-174)C, TNF-α gene G(-308)A and IL-1β gene C(3954)T polymorphisms) and age-at-onset of type 1 diabetes
mellitus (T1DM) in 165 diabetic children (median age: 17 years). Polymorphisms were determined using the
PCR-RFLP method. We found that the age-at-onset of T1DM was significantly different in patients with a
different IL-6 genotype (median age-at-onset of T1DM was: 8, 6 and 4.5 years in children with the (-174)GG, GC
and CC genotypes, respectively; p < 0.01). Adjusted for TNF-α and IL-1β polymorphisms, patients with a IL-6
(-174)CC genotype have a 3.0-fold (95% CI: 1.2-7.1) increased risk of developing diabetes before the age of 6 years
than (-174)G allele carrier patients. However, we found this association to be present only in patients who carried
the TNF-α (-308)A or IL-1β (3954)T allele, i.e. in patients with high TNF-α and high IL-1β producer genotypes.
We suppose that in the case of high TNF-α and IL-1β producer genotypes, elevated proinflammatory cytokine
levels result in a higher production of IL-6 in (-174)G allele carrier patients. This elevated IL-6 level may have a
protective effect against the development of T1DM and may delay the destruction of pancreatic b-cells.},
DOI = {}
}