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


CONCLUSIONS
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).
Uthurralt
Julieta
J
Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA. juthurralt@cnmcresearch.org
Gordish-Dressman
Heather
H
Bradbury
Meg
M
Tesi-Rocha
Carolina
C
Devaney
Joseph
J
Harmon
Brennan
B
Reeves
Erica K
EK
Brandoli
Cinzia
C
Hansen
Barbara C
BC
Seip
Richard L
RL
Thompson
Paul D
PD
Price
Thomas B
TB
Angelopoulos
Theodore J
TJ
Clarkson
Priscilla M
PM
Moyna
Niall M
NM
Pescatello
Linda S
LS
Visich
Paul S
PS
Zoeller
Robert F
RF
Gordon
Paul M
PM
Hoffman
Eric P
EP
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016009:Chi-Square Distribution; D015331:Cohort Studies; D015444:Exercise; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D016014:Linear Models; D008297:Male; D047493:PPAR alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012737:Sex Factors; D050151:Subcutaneous Fat / Q000033:anatomy & histology*; D014280:Triglycerides / Q000097:blood*; D044465:White People
D047493:PPAR alpha; D014280:Triglycerides
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