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

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 PPARalpha 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 PPARalpha L162V is on serum triglycerides, with downstream effects on adiposity and response to training.

CONCLUSION:

Our results on association of PPARalpha 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).

• Authors: Julieta Uthurralt, Heather Gordish-Dressman, Meg Bradbury, Carolina Tesi-Rocha, Joseph Devaney, Brennan Harmon, Erica K Reeves, Cinzia Brandoli, Barbara C Hansen, Richard L Seip, Paul D Thompson, Thomas B Price, Theodore J Angelopoulos, Priscilla M Clarkson, Niall M Moyna, Linda S Pescatello, Paul S Visich, Robert F Zoeller, Paul M Gordon, Eric P Hoffman
• Journal: BMC medical genetics (BMC Med Genet) Vol. 8 Pg. 55 (Aug 16 2007) ISSN: 1471-2350 [Electronic] England
• PMID: 17705849 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• PPAR alpha
• Triglycerides

Topics

• Adolescent
• Adult
• Alleles
• Chi-Square Distribution
• Cohort Studies
• Exercise
• Female
• Genotype
• Humans
• Insulin Resistance (genetics)
• Linear Models
• Male
• PPAR alpha (genetics)
• Polymorphism, Single Nucleotide
• Quantitative Trait, Heritable
• Sex Factors
• Subcutaneous Fat (anatomy & histology)
• Triglycerides (blood)
• White People