IL6 Gene Promoter Polymorphisms and Type 2 Diabetes

Abstract

Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, ؊174G>C(rs1800795) and ؊573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 ؊174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P ‫؍‬ 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 ؊573G>C and type 2 diabetes. The observed association of the IL6 ؊174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding. Diabetes 55:2915-2921, 2006

Association between the Interleukin‐6 Gene −572 C/G Polymorphism and the Risk of Type 2 Diabetes Mellitus: A Meta‐Analysis of 11,681 Subjects

“…Here, we focused on the association between the IL-6 gene −572 C/G polymorphism and T2DM risk due to the scarcity of studies on other SNPs of the IL-6 gene. In 2006, Huth et al (2006) performed a meta-analysis mainly based on unpublished studies and showed that the IL-6 gene −572 C/G polymorphism was not associated with T2DM risk. By comparison, the present meta-analysis obtained a conclusion inconsistent with that study.…”

Obesity and polymorphisms in genes regulating human adipose tissue

“…171,172 The C allele of one polymorphism in the IL6 promoter, ÀG174C, has in different populations been associated with obesity and decreased risk of T2DM. [173][174][175][176] The C allele results in lower IL6 expression. 177 Furthermore, the CÀ174C genotype has been associated with lower energy expenditure and lower rate of whole-body glucose uptake.…”

Imunossenescência: a relação entre leucócitos, citocinas e doenças crônicas

“…39 O estresse crônico provocado no sistema imunitário pode ocasionar o declínio da sensibilidade à insulina, contribuindo para o desenvolvimento da DM2. 40,41 Excesso de TNF-α, por exemplo, induz diminuição sistêmica na produção de receptores para insulina, que contribui para um estado de resistência à ação do hormônio. 42 Esse mecanismo pode explicar a resistência insulínica observada na obesidade, uma vez que a massa gorda secreta TNF-α.…”

“…44 E quando comparados os níveis de IL-6 entre pacientes diabéticos e normais, os estudos mostram valores maiores de IL-6 sérica para os portadores da patologia. 33,41,45 Sob o aspecto genético, a presença de SNPs na região promotora do gene da IL-6 sugere que certos alelos podem ser considerados fatores de risco para o desenvolvimento da DM2. 30 A distribuição dos genótipos da IL-6 é significativamente diferente entre indivíduos diabéticos e não-diabéticos, pois o genótipo GG é predominante em pacientes portadores de DM2, quando comparados com pacientes não-diabéticos.…”