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Interleukin-6 Gene Polymorphism and Lipid Abnormalities in Healthy Subjects

Unitat de Diabetologia, Endocrinologia i Nutricio, University Hospital of Girona "Dr Josep Trueta," 17007 Girona; and Unitat d’Endocrinologia, Hospital of Tarragona "Joan XXIII," Facultat Medicina, Universitat Rovira i Virgili, 43007 Tarragona, Spain

Address correspondence and requests for reprints to: J. M. Fernandez-Real, M.D., Ph.D., Unitat de Diabetologia, Endocrinologia i Nutrició, University Hospital of Girona "Dr Josep Trueta," Carretera de França s/n, 17007 Girona, Spain. E-mail: endocrino{at}htrueta.scs.es

Several lines of evidence indicate that interleukin-6 (IL-6) is involved not only in the hepatic acute phase response but also in adipose tissue metabolism, lipoprotein lipase activity, and hepatic triglyceride secretion. A polymorphism in the IL-6 gene, associated with differences in IL-6 transcription rate, has been recently described. We aimed to study whether this IL-6 gene polymorphism leads to differences in fasting and postglucose load plasma 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 in comparison with carriers of the C allele. However, G carriers showed almost twice plasma triglycerides (1.5 ± 0.9 vs. 0.90 ± 0.37 mmol/L; P = 0.01), very low-density lipoprotein (VLDL)-triglycerides (0.97 ± 0.69 vs. 0.42 ± 0.2 mmol/L; P = 0.002), higher fasting (881 vs. 458 µmol/L; P = 0.01), and postglucose load free fatty acids (299 vs. 90.5 µmol/L; P = 0.03), slightly lower high-density lipoprotein-2 cholesterol (0.25 ± 0.14 vs. 0.39 ± 0.26 mmol/L; P = 0.058), and similar cholesterol and LDL-cholesterol levels than carriers of the C allele. Serum IL-6 levels correlated positively with fasting triglycerides, VLDL-triglycerides, and postload free fatty acids (r = 0.61, 0.65 and 0.60, respectively; P < 0.001) and negatively with high-density lipoprotein-cholesterol (r = -0.42, P < 0.05). A tendency toward higher serum IL-6 levels was observed among G carriers (9.9 ± 6.9 vs. 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 associated 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 to higher IL-6 secretion, are prone to lipid abnormalities. Whether this polymorphism contributes to lipid alterations associated with other metabolic disorders awaits additional studies.

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