Interleukin-6 gene polymorphism and lipid abnormalities in healthy subjects

Several lines of evidence indicate that interleukin-6 (IL-6) is involved no t only in the hepatic acute phase response but also in adipose tissue metab olism, lipoprotein lipase activity, and hepatic triglyceride secretion. A p olymorphism in the IL-6 gene, associated with differences in IL-6 transcrip tion rate, has been recently described. We aimed to study whether this IL-6 gene polymorphism leads to differences in fasting and postglucose load pla sma lipids in healthy subjects. Subjects with G at position - 174 of the IL -6 gene were similar in age, sex, body mass index, and waist to hip ratio i n comparison with carriers of the C allele. However, G carriers showed almo st twice plasma triglycerides (1.5 +/- 0.9 us. 0.90 +/- 0.37 mmol/L; P = 0. 01), very low-density lipoprotein (VLDL)-triglycerides (0.97 +/- 0.69 us. 0 .42 +/- 0.2 mmol/L; P = 0.002), higher fasting (881 us. 458 lambda mol/L; P = 0.01), and postglucose load free fatty acids (299 vs. 90.5 mu mol/L; P = 0.03), slightly lower high-density lipoprotein-2 cholesterol (0.25 +/- 0.1 4 us. 0.39 +/- 0.26 mmol/L; P = 0.058), and similar cholesterol and LDL-cho lesterol levels than carriers of the C allele. Serum IL-6 levels correlated positively with fasting triglycerides, VLDL-triglycerides, and postload fr ee fatty acids (r = 0.61, 0.65 and 0.60, respectively; P < 0.001) and negat ively with high-density lipoprotein-cholesterol (r = -0.42, P < 0.05). A te ndency toward higher serum IL-6 levels was observed among G carriers (9.9 /- 6.9 us. 6.85 +/- 1.7 pg/mL; P = 0.09). The - 174G construct was recently reported to show higher expression of IL-6 in He La cells and was associat ed with higher plasma IL-6 levels than the - 174C allele. Thus, the results of the present study suggest that subjects with the G allele, associated t o higher IL-6 secretion, are prone to lipid abnormalities. Whether this pol ymorphism contributes to lipid alterations associated with ether metabolic disorders awaits additional studies.