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Gluten, HLA Genes, and What Your DNA Can Tell You

Gluten is a group of proteins found in wheat, barley, and rye that gives foods their shape and texture. For most people, gluten is harmless. For others, the immune system can react to gluten and cause symptoms ranging from mild digestive discomfort to more significant immune-driven conditions. Variations in the Human Leukocyte Antigen (HLA) gene complex influence how the immune system recognizes proteins, including gluten. Certain HLA patterns increase the chance that the immune system will mistakenly treat gluten as a threat.

How HLA Genes Affect Gluten Sensitivity

The HLA gene complex helps immune cells decide what is safe and what is dangerous. Specific HLA variants may bind fragments of gluten and present them to immune cells in a way that activates an immune response. That does not mean symptoms are guaranteed; it means there is an increased predisposition. Many people with HLA variants associated with gluten reactions never develop symptoms, and many people who do react to gluten do not have these HLA patterns. Your genetic result is one piece of the overall picture.

Interpreting Your rs7454108 Result

CC — Two effect alleles (higher predisposition)

If you have the CC genotype for rs7454108, you carry two copies of the effect allele. This result indicates a stronger genetic association with immune reactions to gluten. Your HLA gene variants may be more likely to present gluten peptides to the immune system in a way that triggers sensitivity or autoimmune responses. That increases your risk for gluten-related conditions compared with people who do not carry these alleles.

Important points

  • This is a predisposition, not a diagnosis. Many people with CC never develop symptoms.
  • Pay attention to symptoms such as chronic digestive discomfort, unexplained fatigue, nutrient deficiencies, skin changes, or neurological symptoms after eating gluten-containing foods.
  • Discuss testing options with your healthcare provider before making major diet changes. Tests may include specific blood markers and, when appropriate, referral for specialty evaluation.
CT — One effect allele (moderate predisposition)

If you have the CT genotype for rs7454108, you carry one copy of the effect allele. This indicates a moderate increase in genetic predisposition to gluten sensitivity. Your HLA proteins might be somewhat more likely to recognize gluten peptides as foreign, but many people with this genotype tolerate gluten without problems.

Important points

  • Watch for symptoms linked to gluten exposure, especially if you notice changes after consuming wheat, barley, or rye.
  • A single effect allele means a modest increase in risk; lifestyle, gut health, and other genes also matter.
  • If you experience symptoms, discuss testing and diagnostic steps with your clinician before trying strict elimination diets.
TT — Zero effect alleles (lower predisposition)

If you have the TT genotype for rs7454108, you carry two copies of the non-effect allele. This indicates a lower genetic predisposition for an immune response to gluten based on this marker. Your HLA gene complex is less likely to present gluten peptides in a way that triggers immune activation.

Important points

  • Lower genetic risk does not rule out non-immune forms of gluten intolerance or other digestive conditions.
  • If you have symptoms after eating gluten, pursue clinical evaluation to identify causes beyond this genetic marker.
  • Maintain balanced nutrition and monitor how your body responds to different foods.

Dietary Recommendations

Regardless of genotype, the following practical dietary approaches support digestive wellbeing and can help manage or clarify symptoms related to gluten:

  • Focus on whole, minimally processed foods: fruits, vegetables, lean proteins, legumes, nuts, seeds, and naturally gluten-free whole grains like rice, quinoa, millet, and oats certified gluten-free when sensitivity is a concern.
  • If you suspect gluten-related symptoms, do not start a strict gluten-free diet before clinical testing. Some diagnostic tests require ongoing gluten exposure to be accurate.
  • Try a short, monitored elimination only under clinical guidance if testing is not possible. Reintroduce gluten systematically to track symptoms and potential triggers.
  • Prioritize fiber-rich and varied plant foods to support gut microbiome diversity, which can influence how your immune system reacts to food components.

Supplements and Supportive Nutrients

Supplements can help address symptoms and support gut health, but they should not replace medical diagnosis or treatment.

  • Probiotics: strains like Lactobacillus and Bifidobacterium may support a healthier gut barrier and reduce digestive discomfort.
  • Digestive enzymes: broad-spectrum or specific proteases may assist with transient digestion issues, especially when meals are large or highly processed.
  • Vitamin and mineral monitoring: long-term malabsorption in immune-mediated gluten conditions can lead to deficiencies in iron, vitamin D, B12, folate, calcium, and zinc. Test levels if symptoms or risk factors exist.
  • Consider a multivitamin or targeted supplementation only after testing and clinician discussion.

Lifestyle and Gut Health

  • Manage stress: chronic stress affects gut permeability and immune activity. Practices like sleep optimization, mindfulness, moderate exercise, and relaxation can reduce symptom burden.
  • Stay hydrated and include high-fiber foods to support regular digestion and a diverse microbiome.
  • Limit excess alcohol and highly processed foods, which can worsen gut inflammation and disrupt the microbiome.
  • Keep a symptom and food diary to spot patterns between gluten intake and symptoms; include timing, portions, and other foods eaten with gluten-containing items.

Clinical Tests and When to Seek Care

  • If you have persistent digestive symptoms, unexplained anemia, weight loss, or other systemic symptoms, see your healthcare provider for evaluation.
  • Recommended tests may include specific serologic markers for immune-mediated gluten conditions and, if indicated, referral for further gastrointestinal evaluation.
  • Do not self-diagnose based on genetics alone. Genetic predisposition is informative but not determinative.

Practical Next Steps

  • Note any symptoms that occur consistently after eating gluten-containing foods and review them with your clinician.
  • Ask your clinician about appropriate testing before making long-term dietary changes.
  • Consider dietary adjustments focused on whole foods, gut-friendly choices, and targeted supplementation as advised by your provider.
  • Use your genetic result as one part of a personalized approach to health and wellness.

Important Disclaimer

PlexusDx provides educational information about genetic predispositions and does not provide medical advice. This information is not a diagnosis. Always consult with your healthcare provider or a qualified clinician before making medical or lifestyle decisions based on genetic results. Your provider can help interpret these results in the context of symptoms, medical history, and appropriate testing.