What you carry at this position in your DNA and what research says about it.
Metabolic Health Balance: 8/10 evidence, 20 publications.
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Sample genotype (not yours): T/T
Lower LDL Cholesterol but Higher Triglycerides
This genotype presents a distinct metabolic trade-off. It is linked to lower LDL cholesterol and improved insulin sensitivity, but also higher triglycerides and liver enzymes.
What this genotype means: Lower LDL cholesterol; Higher circulating triglycerides; Elevated liver enzyme ALT.
Sample genotype (not yours): C/C
Higher LDL Cholesterol but Lower Triglycerides
This genotype presents a distinct metabolic trade-off. It is linked to higher LDL cholesterol and insulin resistance, but also lower triglycerides and liver enzymes.
What this genotype means: Higher LDL cholesterol; Lower circulating triglycerides; Lower liver enzyme ALT.
Sample genotype (not yours): T/C
Typical Metabolic and Lipid Balance
This genotype represents the intermediate, balanced state. It is associated with typical levels of cholesterol, triglycerides, and liver enzymes.
What this genotype means: Typical cholesterol levels; Typical triglyceride levels; Normal liver enzyme levels.
Gene function and biological role
Gene Function: LOC157273 is a long non-coding RNA gene that acts as a key regulator of metabolic pathways in the liver. It functions by modulating the expression of the nearby PPP1R3B gene, which is essential for glycogen storage. Through this regulatory pathway, the gene influences how the liver processes glucose and packages fats for transport in the bloodstream. Consequently, variations in this region are strongly linked to systemic insulin sensitivity and circulating lipid profiles [1]. This makes the locus a major genetic determinant of overall cardiometabolic health [2].
Variant Impact: The rs2126259 variant is an intronic change within the LOC157273 non-coding RNA gene. This genetic change alters the regulatory activity of the non-coding RNA, directly impacting hepatic glycogen synthesis and lipid secretion. The major C allele is associated with higher levels of circulating cholesterol fractions, including LDL and total cholesterol [3]. Conversely, the minor T allele shifts the metabolic balance, resulting in lower cholesterol but higher circulating triglycerides and liver enzyme levels [4]. This variant represents a classic genetic trade-off between cardiovascular lipid markers and liver fat indicators.
Read on the Carbohydrate Preference page
Key Insight: This variant acts as a metabolic pivot, where genotypes that lower cardiovascular risk markers like LDL cholesterol simultaneously raise liver stress markers like ALT and triglycerides.
Location: PPP1R3B. Chromosome 8 · 8p23.1 · 9.3 Mb
Estimated prevalence by population
Global 2.0%; European 1.0%; African 2.8%; East Asian < 0.1%; South Asian 1.2%; Americas 4.6%; Ashkenazi 0.4%; Finnish 3.1%; Middle Eastern 0.6%; Amish 0.2%.
Estimated TT genotype frequency.
Global 22.3%; European 17.7%; African 28.0%; East Asian 2.5%; South Asian 19.8%; Americas 33.8%; Ashkenazi 11.2%; Finnish 29.2%; Middle Eastern 13.8%; Amish 8.4%.
Estimated TC genotype frequency.
Global 75.8%; European 81.4%; African 69.2%; East Asian 97.5%; South Asian 78.9%; Americas 61.5%; Ashkenazi 88.4%; Finnish 67.7%; Middle Eastern 85.6%; Amish 91.4%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 8/10. Source: PMID 29507422. Lower LDL.
Triglycerides. Evidence: 6/10. Source: PMID 29507422. Higher Triglycerides.
Metabolic Syndrome & Insulin Resistance
Insulin Resistance. Evidence: 5/10. Source: PMID 37291194. Lower Resistance.
Organ Systems
Liver Function & Disease
ALT Liver Enzyme. Evidence: 8/10. Source: PMID 33547301. Higher ALT.
Showing effects for C/C genotype
LDL Cholesterol. Evidence: 8/10. Source: PMID 29507422. Higher LDL.
Triglycerides. Evidence: 6/10. Source: PMID 29507422. Lower Triglycerides.
Insulin Resistance. Evidence: 5/10. Source: PMID 37291194. Higher Resistance.
ALT Liver Enzyme. Evidence: 8/10. Source: PMID 33547301. Lower ALT.
Showing effects for T/C genotype
LDL Cholesterol. Evidence: 8/10. Source: PMID 29507422. Typical LDL.
Triglycerides. Evidence: 6/10. Source: PMID 29507422. Typical.
Insulin Resistance. Evidence: 5/10. Source: PMID 37291194. Typical.
ALT Liver Enzyme. Evidence: 8/10. Source: PMID 33547301. Typical ALT.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Carrying two copies of the minor T allele shifts hepatic metabolism toward lower circulating cholesterol levels. Large-scale genetic studies show that this genotype is associated with significantly lower total cholesterol and LDL cholesterol [1]. Additionally, it correlates with lower insulin resistance, suggesting a more efficient response to glucose [2]. However, this metabolic state also leads to higher circulating triglycerides [1]. It is also associated with elevated levels of alanine aminotransferase (ALT), a liver enzyme that can indicate increased liver fat or cellular stress [3].
Lower LDL cholesterol; Higher circulating triglycerides; Elevated liver enzyme ALT.
Sample genotype: CC (Homozygous)
Carrying two copies of the major C allele promotes a metabolic profile characterized by higher circulating cholesterol. Genome-wide association studies consistently link this genotype to elevated total cholesterol, LDL cholesterol, and intermediate-density lipoproteins [1]. It is also associated with higher insulin resistance, which can affect systemic glucose regulation [2]. On the positive side, this genotype is protective against high triglycerides [3]. Furthermore, it is associated with lower levels of the liver enzyme alanine aminotransferase (ALT), indicating lower liver fat accumulation [4].
Higher LDL cholesterol; Lower circulating triglycerides; Lower liver enzyme ALT.
Sample genotype: TC (Heterozygous)
Having one copy of each allele results in a balanced metabolic profile that sits between the two homozygous extremes. Circulating levels of LDL cholesterol, total cholesterol, and triglycerides are generally close to the population average [1]. Similarly, liver enzyme levels such as alanine aminotransferase (ALT) and markers of insulin sensitivity remain at typical baseline levels [2]. This heterozygous state avoids the elevated cholesterol risk of the C/C genotype, while also avoiding the elevated triglyceride and liver enzyme risks of the T/T genotype [3].
Typical cholesterol levels; Typical triglyceride levels; Normal liver enzyme levels.
Variants with shared genetic architecture
rs4240624 · PPP1R3B Gene · Chr 8 · Gallstone and Cholesterol Risk
rs4841132 · PPP1R3B Gene · Chr 8 · Metabolic Trade-Off
rs6601299 · PPP1R3B Gene · Chr 8 · Cholesterol and Lipids
Genome-wide characterization of circulating metabolic biomarkers.
A large electronic-health-record-based genome-wide study of serum lipids.
Content updated August 2026.
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