PPARα L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

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• 作者：Julieta Uthurralt (1)
  Heather Gordish-Dressman (1)
  Meg Bradbury (1)
  Carolina Tesi-Rocha (1)
  Joseph Devaney (1)
  Brennan Harmon (1)
  Erica K Reeves (1)
  Cinzia Brandoli (1)
  Barbara C Hansen (2)
  Richard L Seip (3)
  Paul D Thompson (3)
  Thomas B Price (3) (4)
  Theodore J Angelopoulos (5)
  Priscilla M Clarkson (6)
  Niall M Moyna (7)
  Linda S Pescatello (8)
  Paul S Visich (9)
  Robert F Zoeller (10)
  Paul M Gordon (11)
  Eric P Hoffman (1)
  
• 刊名：BMC Medical Genetics
• 出版年：2007
• 出版时间：December 2007
• 年：2007
• 卷：8
• 期：1
• 全文大小：1278KB
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  17. Vohl Marie-Claude, Lepage Pierre, Gaudet Daniel, Brewer CarlG, Bétard Christine, Perron Patrice, Houde Ghislaine, Cellier Christine, Faith JanetM, Després Jean-Pierre, Morgan Kenneth, Hudson ThomasJ: Molecular scanning of the human PPARa gene: association of the L162V mutation with hyperapobetalipoproteinemia. / J Lipid Res 2000,41(6):945-2.
  18. Flavell DM, Pineda Torra I, Jamshidi Y, Evans D, Diamond JR, Elkeles RS, Bujac SR, Miller G, Talmud PJ, Staels B, Humphries SE: Variation in the PPAR gene is associated with altered function in vitro and plasma lipid concentrations in type II diabetic subjects. / Diabetologia 2000, 43:673-80. CrossRef
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  27. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/8/55/prepub
  
• 作者单位：Julieta Uthurralt (1)
  Heather Gordish-Dressman (1)
  Meg Bradbury (1)
  Carolina Tesi-Rocha (1)
  Joseph Devaney (1)
  Brennan Harmon (1)
  Erica K Reeves (1)
  Cinzia Brandoli (1)
  Barbara C Hansen (2)
  Richard L Seip (3)
  Paul D Thompson (3)
  Thomas B Price (3) (4)
  Theodore J Angelopoulos (5)
  Priscilla M Clarkson (6)
  Niall M Moyna (7)
  Linda S Pescatello (8)
  Paul S Visich (9)
  Robert F Zoeller (10)
  Paul M Gordon (11)
  Eric P Hoffman (1)
  
  1. Research Center for Genetic Medicine, Children's National Medical Center, 20010, Washington, DC, USA
  2. Obesity, Diabetes and Aging Research Center, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, 33612, Tampa, Florida, USA
  3. Division of Cardiology, Henry Low Heart Center, Hartford Hospital, 06102, Hartford, CT, USA
  4. Department of Diagnostic Radiology, Yale University School of Medicine, 06520, New Haven, CT, USA
  5. Center for Lifestyle Medicine and Department of Health Professions, University of Central Florida, 32816, Orlando, FL, USA
  6. Department of Exercise Science, Totman Building, University of Massachusetts, 01003, Amherst, MA, USA
  7. Department of Sport Science and Health, Dublin City University, Dublin 9, Ireland
  8. School of Allied Health, University of Connecticut, 06269, Storrs, CT, USA
  9. Human Performance Laboratory, Central Michigan University, 48859, Mount Pleasant, Mich, USA
  10. Department of Exercise Science and Health Promotion, Florida Atlantic University, 33314, Davie, FL, USA
  11. Division of Exercise Physiology, School of Medicine, West Virginia University, 26506, Morgantown, WV, USA
  
• ISSN：1471-2350

文摘

Background Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components (typically 50-0% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome. Methods We studied 610 young adult volunteers (average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training. Results We found the PPARα L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes (LL = 116 ± 11 mg/dL, LV = 208 ± 30 mg/dL; p = 0.004). Men with the V allele showed lower HDL (LL = 42 ± 1 mg/dL, LV = 34 ± 2 mg/dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume (LL = -1,707 ± 21 mm3, LV = 17,617 ± 58 mm3 ; p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARα L162V is on serum triglycerides, with downstream effects on adiposity and response to training. Conclusion Our results on association of PPARα and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% (p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males (p = 0.0037).