GSTP1 Ala114Val (rs1138272): Detoxification Gene

The GSTP1 Ala114Val polymorphism (rs1138272) is the second major variant in the glutathione S-transferase Pi gene, affecting enzyme stability and thermal sensitivity. While less common than Ile105Val, this variant can further modify GSTP1 function, particularly when inherited together with other GSTP1 variants. Understanding both variants provides a more complete picture of your GSTP1-mediated detoxification capacity.

Understanding Ala114Val

This variant affects enzyme stability rather than substrate binding:

• C allele (Ala): Alanine at position 114 - wild type, stable enzyme
• T allele (Val): Valine at position 114 - reduced thermal stability

Understanding Your Genotype

• C/C (Ala/Ala): Normal enzyme stability
• C/T (Ala/Val): Intermediate stability
• T/T (Val/Val): Reduced enzyme stability (rare)

Difference from Ile105Val

Functional Effects

Enzyme Stability

• Val114 variant shows reduced thermal stability
• May have faster turnover under stress conditions
• Enzyme more susceptible to degradation
• Could result in lower effective GSTP1 levels

Combined with Ile105Val

• The two variants are often inherited together (linkage disequilibrium)
• Val105-Val114 haplotype (double variant) has compound effects
• Both altered substrate specificity AND reduced stability
• May have more significant functional consequences

GSTP1 Haplotypes

• Ile105-Ala114 (*A): Reference haplotype - normal function
• Val105-Ala114 (*B): Altered substrate specificity
• Val105-Val114 (*C): Altered specificity + reduced stability
• Ile105-Val114 (*D): Rare - stability effect only

Health Implications

Cancer Risk

• Less studied than Ile105Val for cancer associations
• Some studies show additive effects when combined with other variants
• Double variant (*C haplotype) may have higher cancer risk
• Primarily relevant in context of carcinogen exposure

Drug Metabolism

• May affect metabolism of GSTP1-dependent drugs
• Chemotherapy response potentially modified
• Less clinical data available than for Ile105Val

Oxidative Stress Response

• Reduced enzyme stability may impair sustained antioxidant defense
• May be more relevant under conditions of high oxidative stress
• Interaction with environmental factors important

Supporting GSTP1 Function

Glutathione Optimization

Particularly important if you have stability-reducing variants:

• N-Acetyl Cysteine (NAC): 600-1200mg daily supports glutathione
• Glycine: Often limiting for glutathione synthesis
• Selenium: Required for glutathione-related enzymes
• B vitamins: Support methylation and glutathione cycling

Enzyme Induction

• Cruciferous vegetables: Sulforaphane induces GST expression
• Broccoli sprouts: Particularly high in sulforaphane
• Turmeric: May support Phase II enzyme expression
• Green tea: Contains compounds that support detoxification

Reduce Oxidative Burden

• Minimize exposure to toxins and carcinogens
• Adequate antioxidant intake from colorful fruits and vegetables
• Avoid excessive alcohol (depletes glutathione)
• Don't smoke

Prevalence

• Val (T) allele frequency: Approximately 10-15% in most populations
• Val/Val genotype: Rare (~1-2%)
• Often co-inherited: With Val105 due to linkage disequilibrium

Clinical Relevance

When This Matters Most

• Combined with Ile105Val variant
• High toxin/carcinogen exposure situations
• Chemotherapy treatment planning
• Chronic oxidative stress conditions

Testing Considerations

• Often tested alongside Ile105Val
• Haplotype analysis more informative than single variant
• Consider other GST genes (GSTM1, GSTT1) for complete picture

Testing with NutraHacker

NutraHacker's Complete Mutation Report analyzes both GSTP1 variants along with other detoxification genes, giving you a comprehensive understanding of your Phase II detox capacity.

Frequently Asked Questions

Is this variant as important as Ile105Val?

Ile105Val is more extensively studied and has clearer functional effects on substrate specificity. Ala114Val is less common and primarily affects enzyme stability. However, when both variants are present together (the *C haplotype), the combined effect may be more significant than either alone. Analyzing both gives the most complete picture.

What if I have both Val105 and Val114?

The double variant haplotype (*C) combines altered substrate specificity with reduced enzyme stability. This may result in more compromised GSTP1 function overall. If you have this combination, paying extra attention to glutathione support, antioxidant intake, and toxin avoidance is particularly sensible.

How common is it to have both variants?

Due to linkage disequilibrium (the variants tend to be inherited together), the Val105-Val114 combination is more common than random chance would predict. About 5-10% of people of European ancestry carry this haplotype. Your genetic test results will show both variants.

References

1. Ali-Osman F, et al. Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. J Biol Chem. 1997;272(15):10004-10012.
2. Hu X, et al. Glutathione S-transferase polymorphisms and cancer risk: a meta-analysis. Pharmacogenet Genomics. 2005;15(7):707-715.
3. McIlwain CC, et al. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene. 2006;25(11):1639-1648.