Effects of polymorphisms in nucleotide-binding oligomerization domains 1 and 2 on biomarkers of the metabolic syndrome and type II diabetes.

The innate immune receptor toll-like receptor 4 (TLR4) has been implicated in mediating some of the effects of dietary lipids on inflammation and type 2 diabetes (T2D). Similar to TLR4, the nucleotide-binding oligomerization domains (Nods) 1 and 2 are also proteins of innate immunity, which can respond to lipids and initiate pro-inflammatory signalling that plays a role in the aetiology of T2D. The objective was to determine the effect of Nod1 (Glu266Lys) and Nod2 (Ser268Pro) genotypes on factors associated with the metabolic syndrome (MetS), and whether they modify the association between dietary lipids and biomarkers of the MetS. Men and women (n = 998) between the ages of 20-29 years were genotyped for both polymorphisms, completed a one-month, semiquantitative food frequency questionnaire and provided a fasting blood sample. The Glu266Lys polymorphism in Nod1 was not associated with any of the biomarkers of the MetS, but modified the association between dietary saturated fat (SFA) and insulin sensitivity, as measured by HOMA-IR (p for interaction = 0.04). Individuals with the Glu/Glu or Glu/Lys genotype showed no significant relationship between dietary SFA and HOMA-IR (β = -0.002 ± 0.006, p = 0.77; and β = -0.003 ± 0.006, p = 0.61), while those with the Lys/Lys genotype showed a positive association (β = 0.033 ± 0.02, p = 0.03). The Nod2 Ser268Pro polymorphism was not associated with components of the MetS and did not modify the relationship between dietary lipid intake and the biomarkers of MetS. In summary, the Nod1 Glu266Lys polymorphism modifies the relationship between dietary SFA intake and HOMA-IR, suggesting that Nod1 may act as an intracellular lipid sensor affecting insulin sensitivity.