Introduction Type 2 diabetes mellitus (T2DM) has been linked to a state of chronic inflammation due to innate immunity. Serum levels of pro-inflammatory cytokines are elevated in the early stages of T2DM and increase with disease progression. Genetic variation can affect the innate immune response to environmental factors, and may determine an individual's risk of disease.

Methods We conducted a cross-sectional study in 7384 subjects from the TwinsUK Registry to evaluate the association between 18 single nucleotide polymorphisms (SNPs) in five genes (TLR4, IL1A, IL6, TNFA, and CRP) along the innate immunity-related inflammatory pathway and biomarkers of predisposition to T2DM [fasting insulin and glucose, HDL- and LDL- cholesterols, triglycerides (TGs), amyloid-A, sensitive C reactive protein (sCRP) and vitamin D binding protein (VDBP) and body mass index (BMI)].

Results Of the 18 SNPs examined (18 SNPs with 9 phenotypes), 14 were significantly associated with a metabolic risk factors for T2D (P£0.0027). Fasting insulin was associated with SNPs in IL6, TLR4 and TNFA, whereas serum LDL-C was associated with variants of IL1A and IL6. Serum CRP level was associated with SNPs in IL1A, IL6, TLR4 and CRP. Correlation among the different factors related to risk of T2DM showed a significant (p<0.0001) positive correlation between BMI and glucose (r=0.22), insulin (r=0.23), amyloid-A (r=0.23), sCRP (r=0.37), LDL-C (r=0.09) and TGs (r=0.32).

Conclusion Genetic variants in the innate immunity pathway are associated with biomarkers of T2DM and metabolic syndrome, an observation that may provide a rationale for studying their use in early disease risk prediction.