The aim of this study was to examine the effects of omega-3 fatty acids on novel cardiovascular risk factors in relation to +174 G>C interleukin-6 gene (IL6) single nucleotide polymorphism (SNP).

A total of 61 patients (M/F: 34/27; age 53.9±1.2 yrs; BMI 32.68±0.77kg/m²; HbA1С 7.06±0.18%; FBG 8.00±0.28mmol/L) with Type 2 diabetes mellitus (T2D) were treated with omega-3 fatty acids (1-g capsule containing at least 900mg of ethyl esters of eicosapentaenoic and docosahexaenoic acids, daily) for 12 weeks without changing any of their previous medications. In all the +174 G>C (rs1800795) SNP in IL6 was determined by PCR-RFLP. There were estimated plasma total and high molecular weight adiponectin (HMWA), insulin, leptin, osteoprotegerin (OPG), retinol-binding protein-4 (RBP4), fetuin-A, vaspin levels etc. by ELISA in the basal state and after the treatment. Insulin resistance (IR) was assessed using homeostasis model assessment (HOMA-IR) algorithm. Unpaired Student's t-test, Fisher's test and Chi² test were used. Data are expressed as mean±SEM or median (25;75).

Comparing with controls (n=21) T2D patients were characterized by significant (P<0.05–0.0001) IR, hypoadiponectinemia (total and HMW), increase in plasma NEFA, triglycerides, OPG, RBP4, and fetuin-A levels, decrease in antioxidative defense (erythrocyte reduced glutathione concentrations). It was revealed, that the pro-atherogenic homozygous GG-genotype carriers as compaired to GC heterozygotes and CC homozygotes demonstrated the widest range and pronounced beneficial effects of adjunctive therapy, namely, a significant improvement in long-term glycemic control, reducing dyslipidemia, increased levels of anti-atherogenic HMWA, increased antioxidant protection (erythrocyte reduced glutathione). Carriers of the G allele showed a significant reduction in IL-6 levels in the circulation after consumption of omega-3 fatty acids [5.94μg/L (5.18;7.56) vs. 7.61μg/L (6.34;10.4), P<0.05].

Our data show the role of +174 G>C IL6 SNP in omega-3 fatty acid therapeutic efficacy forming in type 2 diabetics with respect to new cardiovascular risk factors (adipocytokines, antioxidant protection) with the indication of GG-genotype as the most reactive. These results confirm the perspective of pharmacogenetics as a basis for personalized therapy with the predicted effect of pharmacological intervention.