rs35767 — IGF1 C-1245T

Promoter variant affecting circulating IGF-1 levels and athletic performance potential

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The Anabolic Switch — IGF-1 and Your Muscle-Building Potential

Insulin-like growth factor 1 (IGF-1) is one of the most powerful anabolic hormones in the human body. It activates the PI3K/Akt/mTOR pathway11 activates the PI3K/Akt/mTOR pathway
The canonical growth signaling cascade that controls muscle protein synthesis and hypertrophy, stimulates satellite cell activation22 satellite cell activation
Muscle stem cells that divide and fuse to repair damage and create new muscle tissue, and drives skeletal muscle hypertrophy in response to training. The rs35767 polymorphism sits in the promoter region of the IGF1 gene, 1,245 base pairs upstream of the transcription start site, where it regulates how much IGF-1 your body produces.

The A allele is associated with higher circulating IGF-1 levels compared to the C allele, and AA carriers tend to have greater muscle mass and superior athletic performance33 greater muscle mass and superior athletic performance
Particularly in power and combined power-endurance sports like decathlon. This variant has emerged as one of the most replicated genetic markers for elite athletic performance.

The Mechanism

rs35767 is a regulatory variant located in the promoter region of the IGF1 gene on chromosome 12. The T-to-C substitution at position -1245 affects transcription factor binding and gene expression. Studies show the A allele leads to higher IGF-1 production, though the exact transcription factor interactions remain under investigation. Some research suggests the G allele may allow binding of C/EBPD transcription activator44 G allele may allow binding of C/EBPD transcription activator
A DNA-binding protein that regulates gene expression, while other evidence indicates the A allele results in higher circulating levels through mechanisms that may involve altered promoter activity.

Once IGF-1 is secreted (primarily by the liver in response to growth hormone), it binds to IGF-1 receptors on muscle cells. This triggers a signaling cascade: PI3K converts PIP2 to PIP3, activating PDK1 and Akt. Akt then phosphorylates mTORC1, which activates ribosomal protein S6 and translation initiation factor eIF4E, ramping up protein synthesis. Simultaneously, Akt inhibits FoxO transcription factors, blocking the expression of muscle atrophy genes55 blocking the expression of muscle atrophy genes
E3 ubiquitin ligases like atrogin-1 and MuRF1 that tag muscle proteins for degradation.

IGF-1 also activates muscle satellite cells—the stem cells responsible for muscle repair and growth. After intense exercise or muscle damage, satellite cells proliferate and differentiate into new myonuclei, contributing approximately half of the muscle mass gained during hypertrophy66 half of the muscle mass gained during hypertrophy
Based on studies using viral IGF-1 delivery in animal models.

The Evidence

The rs35767 variant has been studied extensively in athletic populations. In a 2013 Israeli study of 87 power athletes and 78 endurance athletes77 2013 Israeli study of 87 power athletes and 78 endurance athletes
Including international and Olympic-level competitors, the A allele was significantly more frequent in top-level power athletes compared to national-level athletes. Among the elite power cohort, 4.8% carried the TT genotype versus 0% in non-athletic controls—a striking overrepresentation.

A 2022 study of decathlon athletes88 2022 study of decathlon athletes
Decathlon demands both power and endurance across 10 events found the AA genotype was significantly more prevalent among decathletes compared to other athlete groups, and AA carriers demonstrated superior speed performance. These findings align with the physiological role of IGF-1 in fast-twitch muscle fiber development and force production.

A 2024 meta-analysis99 2024 meta-analysis
Pooling data across multiple cohorts to increase statistical power confirmed the A allele as a favorable genetic marker for both power and endurance athletic performance, supporting the variant's role across multiple training modalities.

At the molecular level, a 2014 study of European adults1010 2014 study of European adults
n=569 in discovery cohort measured circulating IGF-1 and found that carriers of the GG genotype (equivalent to TT on the minus strand) had significantly higher IGF-1 levels (218 ng/ml) compared to AA carriers (190 ng/ml, p=0.007). The higher IGF-1 group also showed better insulin sensitivity, suggesting metabolic benefits beyond muscle growth.

However, not all effects are beneficial. A Japanese longitudinal cohort of 1,506 individuals1111 Japanese longitudinal cohort of 1,506 individuals
Followed for long-term health outcomes found that AA carriers experienced faster decline in renal function over time compared to GG carriers, suggesting chronically elevated IGF-1 may have tradeoffs for kidney health.

Practical Actions

If you carry one or two A alleles, you have a genetic advantage for building muscle and responding to strength training. To capitalize on this:

Prioritize resistance training. Your elevated IGF-1 levels mean you're biochemically primed for hypertrophy. Focus on progressive overload—gradually increasing weight, volume, or intensity over time. AA carriers may see faster strength gains and better recovery from high-volume training compared to CC carriers.

Consume adequate protein. IGF-1 activates mTOR, the master regulator of protein synthesis, but mTOR needs amino acid availability to function. Aim for 1.6-2.2 g/kg body weight daily, with post-workout protein intake1212 post-workout protein intake
20-40g within 2 hours of training to maximize the anabolic window when IGF-1 signaling is elevated.

Optimize sleep and recovery. Growth hormone (the primary driver of hepatic IGF-1 production) peaks during deep sleep. AA carriers producing more IGF-1 may benefit even more from adequate sleep (7-9 hours) for muscle repair and satellite cell activation.

Consider monitoring kidney function if you're TT. While the athletic benefits are clear, the Japanese cohort data suggests potential long-term renal effects. If you're a TT carrier pursuing intense athletic training, periodic monitoring of eGFR and creatinine may be prudent, especially as you age or if you have other kidney risk factors.

Interactions

rs35767 interacts with other variants in the IGF axis. rs71364461313 rs7136446
An intronic IGF1 variant has also been associated with athletic performance and may compound with rs35767 to influence IGF-1 levels and muscle phenotype. Similarly, rs9729361414 rs972936
Another IGF1 intronic variant affects IGF-1 expression and has been linked to neurological outcomes and muscle force production.

Beyond the IGF1 gene, interactions with the growth hormone receptor and myostatin pathway are likely. Carriers of both the IGF1 A allele and myostatin rare R allele1515 myostatin rare R allele
Loss-of-function variants in MSTN that reduce this muscle growth inhibitor show even greater muscle mass and performance, suggesting an additive or synergistic effect.

For power athletes, the combination of rs35767 TT and ACTN3 RR1616 ACTN3 RR
Alpha-actinin-3, the "gene for speed" may represent an elite genetic profile for explosive strength and sprint performance.

Nutrient Interactions

protein altered_metabolism

Genotype Interpretations

What each possible genotype means for this variant.

AG Intermediate IGF-1 Producer Intermediate

Moderate IGF-1 levels with balanced anabolic potential

The GA genotype represents a codominant effect where you produce intermediate levels of IGF-1. While the 2014 European study grouped CT and AA carriers together (showing higher IGF-1 than CC), other research suggests GA carriers fall between the two homozygous groups. Your IGF-1 signaling is sufficient to support robust muscle protein synthesis and satellite cell activation, but you may not see the extreme power athlete phenotype observed in AA carriers.

This intermediate position may be metabolically optimal—you get substantial anabolic benefits without the highest IGF-1 levels that have been linked to faster renal decline and potentially elevated cancer risk. The GA genotype appears in successful athletes across multiple sports, suggesting it's compatible with elite performance.

From a practical standpoint, GA carriers respond predictably to resistance training. You're not at a significant disadvantage compared to AA carriers, especially when training, nutrition, and recovery are optimized.

GG Lower IGF-1 Producer Reduced

Lower circulating IGF-1 levels and reduced anabolic signaling

The GG genotype at rs35767 is associated with reduced IGF-1 gene expression from the promoter region. In the 2014 European study, GG carriers (referred to as AA on the opposite strand) had mean IGF-1 levels of 190 ng/ml versus 218 ng/ml in AA carriers (p=0.007). Lower IGF-1 means reduced activation of the PI3K/Akt/mTOR pathway and potentially less robust satellite cell activation following resistance training.

However, IGF-1 is only one piece of the muscle-building puzzle. Training stimulus, nutrition, sleep, and other genetic factors (myostatin, ACTN3, PPARGC1A) also play critical roles. GG carriers can absolutely build significant muscle and strength—they may simply need to be more strategic about training program design and recovery.

The lower IGF-1 levels may also confer protection against certain diseases. High IGF-1 has been associated with increased cancer risk and potentially faster cellular aging, so the GG genotype may offer longevity benefits that offset the athletic disadvantages.

AA High IGF-1 Producer High

Elevated IGF-1 levels associated with superior athletic performance and hypertrophy potential

The AA genotype represents the optimal IGF1 promoter configuration for anabolic signaling. You produce more IGF-1 from the same growth hormone stimulus, leading to enhanced activation of the PI3K/Akt/mTOR pathway, stronger suppression of muscle atrophy genes, and more robust satellite cell activation. This translates to faster muscle growth, better recovery, and superior training adaptations.

The athletic data is striking: among Israeli power athletes, AA carriers were found exclusively at the international/Olympic level, with zero AA carriers in the general population controls. Decathlon athletes showed the highest TT prevalence, and AA carriers in this group had superior speed performance. The 2024 meta-analysis confirmed the A allele favors both power and endurance sports.

However, the Japanese cohort data introduces an important caveat: AA carriers experienced faster long-term decline in estimated glomerular filtration rate (eGFR), a marker of kidney function. The mechanism isn't fully understood, but chronically elevated IGF-1 may increase glomerular hyperfiltration or contribute to renal hypertrophy. This doesn't mean AA carriers will develop kidney disease, but it suggests monitoring may be prudent, especially for athletes engaged in years of intense training or using high protein intakes.