The rs1800629 Polymorphism in the TNF Gene Interacts with Physical Activity on the Changes in C-reactive Protein Levels in the Finnish Diabetes Prevention Study

Abstract

Physical activity exerts anti-inflammatory effects, but genetic variation may modify its influence. In particular, the rs1800629 single-nucleotide polymorphism (SNP) in the tumor necrosis factor (TNF) gene and the rs1800795 SNP in the interleukin-6 (IL6) gene have been found to modify the effect of exercise training on circulating levels of C-reactive protein (CRP) and IL-6, respectively. We assessed whether rs1800629 and rs1800795 modified the effect of moderate-to-vigorous physical activity on changes in serum levels of high-sensitivity CRP and IL-6 in the Finnish Diabetes Prevention Study (DPS). Genotype and 1-year data on changes in physical activity, serum CRP and IL-6 were available for 390 overweight subjects with impaired glucose tolerance. The rs1800629 SNP in TNF interacted with the 1-year change in moderate-to-vigorous physical activity on changes in CRP among those who had high (≥3 mg/L) baseline CRP levels (P=0.034 for interaction). Carriers of the GG genotype showed a greater decrease in CRP with increasing physical activity than the individuals with the A allele. No interaction between the rs1800795 SNP in IL6 and changes in moderate-to-vigorous physical activity on the 1-year change in serum IL–6 was found. In conclusion, the rs1800629 SNP in the TNF gene may modify the effect of moderate-to-vigorous physical activity on serum levels of CRP.

Key words

immunology - C-reactive protein - interleukin-6 - tumor necrosis factor-alpha - exercise - genes

References

• 1 Eriksson J, Lindström J, Valle T. et al . Prevention of type II diabetes in subjects with impaired glucose tolerance: The Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme.  Diabetologia. 1999;  42 793-801
• 2 Herder C, Peltonen M, Koenig W. et al . Anti-inflammatory effect of lifestyle changes in the Finnish Diabetes Prevention Study.  Diabetologia. 2009;  52 433-442
• 3 Kolb H, Mandrup-Poulsen T. An immune origin of type 2 diabetes?.  Diabetologia. 2005;  48 1038-1050
• 4 Kroeger KM, Carville KS, Abraham LJ. The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription.  Mol Immunol. 1997;  34 391-399
• 5 Laaksonen DE, Lindström J, Lakka TA. et al . Physical activity in the prevention of type 2 diabetes. The Finnish Diabetes Prevention Study.  Diabetes. 2005;  54 158-165
• 6 Lakka HM, Lakka TA, Rankinen T. et al . The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: The HERITAGE Family Study.  Vascul Pharmacol. 2006;  44 377-383
• 7 Lakka TA, Lakka HM, Rankinen T. et al . The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: The HERITAGE Family Study.  Eur Heart J. 2005;  26 2018-2025
• 8 Oberbach A, Lehmann S, Kirsch K. et al . Long term exercise training decreases IL-6 serum levels in subjects with impaired glucose tolerance: effect of the -174G/C variant in interleukin-6 gene.  Eur J Endocrinol. 2008;  159 129-136
• 9 Petersen AM, Petersen BK. The anti-inflammatory effect of exercise.  J Appl Physiol. 2005;  98 1154-1162
• 10 Starkie R, Ostrowski SR, Jauffred S. et al . Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans.  FASEB J. 2003;  17 884-886

Correspondence