Submitted on October 5, 2006
Accepted on January 23, 2007
Peroxisome Proliferator-Activated Receptor Delta Polymorphisms Are Associated With Physical Performance and Plasma Lipids: The HERITAGE Family Study
Arto J Hautala1, Arthur Leon2, James S. Skinner3, D.C. Rao4, Claude Bouchard5, and Tuomo Rankinen6*
1 Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States; Department of Exercise and Medical Physiology, Merikoski Rehabilitation and Research Centre, Kasarmintie 13, P.O. Box 404, Oulu, Fin-90101 Oulu, Finland
2 School of Kinesiology, University of Minnesota, Minneapolis, Minnesota, United States
3 Kinesiology, Indiana University, Bloomington, Indiana, United States
4 Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, United States; Departments of Genetics and Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States
5 Executive Director, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
6 Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
* To whom correspondence should be addressed. E-mail: rankint{at}pbrc.edu.
We tested the hypothesis that peroxisome proliferator-activated receptor delta (PPARD) gene polymorphisms are associated with cardiorespiratory fitness and plasma lipid responses to endurance training. Associations between the PPARD Exon 4 +15 C/T and Exon 7 +65 A/G polymorphisms and maximal exercise capacity and plasma lipid responses to 20 weeks of endurance training were investigated in healthy White (n=477) and Black (n=264) subjects. In Blacks, the Exon 4 +15 C/C homozygotes showed a smaller training-induced increase in VO2max (P=0.028) than the C/T and T/T genotypes. Similarly, a lower training response in maximal power output was observed in the Exon 4 +15 C/C homozygotes (P=0.005) as compared to the heterozygotes and the T/T homozygotes in Blacks, and a similar trend was evident in Whites (P=0.087). In Whites, baseline apolipoprotein A-1 levels (ApoA-1) were higher in the Exon 4 +15 C/C (P=0.011) and Exon 7 +65 G/G (P=0.05) genotypes compared to the other genotypes. In Whites, Exon 4 +15 C/C (P=0.0025) and Exon 7 +65 G/G (P=0.011) genotypes showed significantly greater increases in plasma high-density lipoprotein cholesterol (HDL-C) levels with endurance training than the other genotypes, whereas in Blacks the Exon 4 +15 CC homozygotes tended to increase (P=0.057) their ApoA-1 levels more than the T allele carriers. DNA sequence variation in the PPARD locus is a potential modifier of changes in cardiorespiratory fitness and plasma HDL cholesterol in healthy individuals in response to regular exercise.
