Title

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

Authors

Authors

J. Uthurralt; H. Gordish-Dressman; M. Bradbury; C. Tesi-Rocha; J. Devaney; B. Harmon; E. K. Reeves; C. Brandoli; B. C. Hansen; R. L. Seip; P. D. Thompson; T. B. Price; T. J. Angelopoulos; P. M. Clarkson; N. M. Moyna; L. S. Pescatello; P. S. Visich; R. F. Zoeller; P. M. Gordon;E. P. Hoffman

Comments

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Abbreviated Journal Title

BMC Med. Genet.

Keywords

PROLIFERATOR-ACTIVATED RECEPTOR; METABOLIC SYNDROME; MUSCLE STRENGTH; GENE; POLYMORPHISM; ASSOCIATION; MUTATION; OBESITY; SIZE; ATHEROSCLEROSIS; Genetics & Heredity

Abstract

Background: Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components ( typically 50 - 80% 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 PPARa 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 mm(3), LV = 17,617 +/- 58 mm(3); p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARa L162V is on serum triglycerides, with downstream effects on adiposity and response to training. Conclusion: Our results on association of PPARa 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).

Journal Title

Bmc Medical Genetics

Volume

8

Publication Date

1-1-2007

Document Type

Article

Language

English

First Page

11

WOS Identifier

WOS:000250533300001

ISSN

1471-2350

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