rs4253778

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This is a intron variant variant in the PPARA gene.

Key Literature Trait Associations

Power vs Endurance Athletic Performance

rs4253778 in PPARα (peroxisome proliferator-activated receptor alpha) influences fatty acid oxidation capacity in skeletal muscle and heart. The C allele is associated with reduced PPARα transcriptional activity and is over-represented in power/sprint athletes, while the G allele (higher fat oxidation) is enriched in endurance athletes. PPARα regulates expression of genes involved in fatty acid transport and beta-oxidation, directly affecting the muscle's fuel preference during exercise.

Lopez-Leon S et al. “Sports genetics: the PPARA gene and athletes' high ability in endurance sports. A systematic review and meta-analysis.” Biology of Sport (2016)

Allele C

OR 1.65

p —

N 2,552

Meta-analysis

European

Barber MD et al. “The response of leptin, interleukin-6 and fat oxidation to feeding in weight-losing patients with pancreatic cancer.” British Journal of Cancer 90(6):1129-1132 (2004)

Allele C

OR —

p 5.0e-3

Candidate gene study

Maciejewska-Skrendo A et al. “Does the PPARA Intron 7 Gene Variant (rs4253778) Influence Performance in Power/Strength-Oriented Athletes? A Case-Control Replication Study in Three Cohorts of European Gymnasts.” Journal of Human Kinetics (2021)

Allele C

OR 3.33

p 2.2e-2

N 464

Candidate gene study

European

Kazancı D et al. “PPARA and IL6: exploring associations with athletic performance and genotype polymorphism.” Cellular and Molecular Biology (noisy-le-grand, France) (2023)

Allele C

OR —

p —

N 30

Candidate gene study

European

Ahmetov II et al. “Current Progress in Sports Genomics.” Advances in Clinical Chemistry (2015)

Allele C

OR —

p —

Candidate gene study

multi-ancestry

Semenova EA et al. “Genes and Athletic Performance: The 2023 Update.” Genes (2023)

Allele C

OR —

p —

Candidate gene study

multi-ancestry

LDL cholesterol

The rs4253778 C allele has been associated with higher total cholesterol and LDL cholesterol in two independent studies. A candidate-gene study in 240 Mexican women found significant associations with total cholesterol (p=0.034) and LDL-C (p=0.037) for the C allele. A separate training intervention study in 168 Polish women found that CC homozygotes experienced unfavorable LDL increases following 12 weeks of aerobic training, whereas other genotypes showed the expected beneficial lipid response. These findings suggest PPARα signaling through this intronic variant may modulate lipid metabolism, particularly in women, though replication in larger studies is needed.

Ortega-Meléndez AI et al. “PPARα polymorphisms association with total cholesterol and LDL-C levels in a Mexican population.” European Review for Medical and Pharmacological Sciences (2022)

Allele C

OR —

p 3.7e-2

N 240

Candidate gene study

Mexican

Maciejewska-Skrendo A et al. “The Polymorphisms of the Peroxisome-Proliferator Activated Receptors' Alfa Gene Modify the Aerobic Training Induced Changes of Cholesterol and Glucose.” Journal of Clinical Medicine (2019)

Allele C

OR —

p —

N 168

Candidate gene study

European

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Research that mentions this SNP (1)

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The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes

AssociationN=2,555Ildus I. Ahmetov et al.(2009)· Human Genetics

This case-control study of 1,423 Russian athletes and 1,132 controls examined 15 metabolic gene polymorphisms associated with elite endurance athlete status. Ten 'endurance alleles' were identified: rs4253778 (PPARA), rs2016520 (PPARD), rs8192678 (PPARGC1A), rs7732671 (PPARGC1B), rs1937 (TFAM), rs660339 (UCP2), rs1800849 (UCP3), rs2010963 (VEGFA), NFATC4 rs2229309, and PPP3R1 promoter 5I. The proportion of subjects with ≥9 endurance alleles was significantly higher in elite endurance athletes versus controls (85.7% vs 37.8%, P=7.6×10⁻⁶). The number of endurance alleles positively correlated with slow-twitch muscle fiber proportion (r=0.50, P=4.0×10⁻⁴) and maximal oxygen consumption (r=0.46, P=7.0×10⁻⁴).

Traits studied:Elite endurance athlete statusMaximal oxygen consumption (VO2max)Slow-twitch muscle fiber proportion

rs4253778

Key Literature Trait Associations

Power vs Endurance Athletic Performance

LDL cholesterol

Research that mentions this SNP (1)

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