Substantial evidence indicates that plasma lipoprotein-lipid levels are related to cardiovascular disease, are highly variable among individuals, and have a strong genetic component. They are also modifiable with exercise training, and these responses are heritable. A small body of literature suggests an association between the interleukin-6 (IL6) 174G/C gene polymorphism and plasma lipoprotein-lipid levels such that the G allele may be associated with a more pro-atherogenic lipid profile than the C allele. We hypothesized that the IL6 174G/C gene polymorphism would be associated with variation in plasma lipoprotein-lipid profiles at baseline and with their response to exercise training.

Sixty-five sedentary, healthy 50- to 75-year-old Caucasians were studied before and after 24 weeks of aerobic exercise training. Significant differences existed among genotype groups for change with exercise training in high-density lipoprotein (HDL)-C, HDL3-C, HDL5NMR-C, HDL4NMR-C, integrated HDL4,5NMR -C, and HDLsize. For HDL-C, the CC group increased significantly more than both the GG (7.0 ± 1.3 v. 1.0 ± 1.1 mg/dL, p=0.001) and the GC group (3.3 ± 0.9 mg/dL, p=0.02). For HDL3-C, the CC group increased significantly more than both the GG (6.1 ± 1.0 v. 0.9 ± 0.9, mg/dL p<0.001) and the GC group (2.5 ± 0.7 mg/dL, p=0.006). For HDL5NMR-C, the GC group increased significantly less than both the CC and GG groups (0.0 ± 0.7 v. 3.4 ± 1.0 mg/dL, p=0.02 and 1.4 ± 0.8 mg/dL, p=0.04). For HDL4NMR-C, the GG group changed significantly differently from both the GC and CC groups with the GG group decreasing and the GC and CC groups increasing HDL4NMR-C (-0.4 ± 1.1 v. 3.1 ± 0.9 mg/dL, p=0.02 and v. 3.2 ± 1.3 mg/dL, p=0.05, respectively). For integrated HDL4,5-C, the CC group increased significantly more than the GG group (6.5 ± 1.6 mg/dL v. 1.0 ± 1.3 mg/dL, p=0.01). For HDLsize, the CC group increased significantly more than both the GG (0.3 ± 0.1 v. 0.1 ± 0.1 nm, p=0.02) and the GC groups (0.0 ± 0.0 nm, p=0.007). These findings suggest that the IL6-174G/C polymorphism influences HDL-C and HDL-C subfraction changes with exercise training.