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Understanding Gluten and Your Genes

Gluten is a group of proteins found in wheat, rye, and barley that give many foods their texture and structure. Most people digest gluten without problems, but certain variations in the Human Leukocyte Antigen or HLA genes can increase the chance of an immune reaction to gluten. HLA genes help the immune system tell the difference between the body s own cells and foreign substances. Specific HLA variants, including types associated with HLA-DQ2 and HLA-DQ8, are commonly found in people with celiac disease and can make the immune system mistakenly attack intestinal tissue when gluten is consumed.

How to Read This Genetic Result

This report focuses on the rs7775228 variant in the HLA region. Your genotype at this location is one piece of information about your genetic predisposition to gluten-related immune reactions. It does not diagnose celiac disease or confirm that symptoms are caused by gluten. Genetic risk interacts with other genes, environment, gut health, and lifestyle. Use this information as a guide for conversation with your healthcare provider.

Two effect alleles (CC) — Higher genetic risk

If your genotype is CC at rs7775228, you carry two copies of the effect allele. This pattern is associated with a stronger genetic link to gluten intolerance and a higher likelihood of immune activation in response to gluten. This variant is located in the HLA gene region, which helps the immune system distinguish self from nonself. The CC genotype is often linked to HLA types such as HLA-DQ2 or HLA-DQ8, which are present in nearly all people diagnosed with celiac disease.

What this means for you

  • Increased genetic predisposition to celiac disease or immune-mediated gluten sensitivity.
  • Greater likelihood that consuming gluten could trigger inflammation or intestinal injury, if disease develops.
  • Genetic risk alone does not confirm diagnosis. Clinical testing and evaluation are needed.
One effect allele (TC) — Moderate genetic risk

If your genotype is TC at rs7775228, you carry one copy of the effect allele. This indicates a moderate increase in genetic predisposition to gluten sensitivity compared with people who do not carry the effect allele. The HLA complex helps the immune system identify foreign proteins. With one effect allele, the immune system may show an increased tendency to react to gluten but the risk is less than with two effect alleles.

What this means for you

  • Some increased genetic susceptibility to gluten-related immune responses.
  • Many people with this genotype tolerate gluten without symptoms. Risk is influenced by other genes and environmental factors.
  • If you have symptoms, consider clinical evaluation and conversation with your provider about testing options.
No effect alleles (TT) — Lower genetic risk

If your genotype is TT at rs7775228, you carry two copies of the non-effect allele. This result indicates a lower genetic predisposition to immune reactions to gluten. Your HLA profile does not include the specific high-risk variants most strongly linked to celiac disease, such as HLA-DQ2 and HLA-DQ8.

What this means for you

  • Lower genetic risk for celiac disease and other HLA-mediated gluten sensitivity compared to carriers of the effect allele.
  • A typical immune response to gluten is more likely, but non-HLA factors can still cause symptoms related to food intolerance or irritable bowel conditions.
  • If you experience digestive symptoms, clinical evaluation can help identify the cause.

Symptoms and When to Seek Clinical Evaluation

  • Common symptoms that may be related to gluten immune reactions: chronic diarrhea, constipation, gas, bloating, abdominal pain, unexplained weight loss, fatigue, iron deficiency, and dermatitis herpetiformis.
  • If you have persistent digestive symptoms, signs of nutrient deficiency, or a family history of celiac disease, talk to your healthcare provider before changing your diet.
  • Do not start a gluten-free diet before clinical testing for celiac disease is complete, because removing gluten can affect test accuracy.

Dietary Recommendations

Whether your genetic risk is higher, moderate, or lower, these dietary approaches support digestive wellbeing and can help manage symptoms.

  • Balanced whole foods: Emphasize vegetables, fruits, legumes, lean proteins, nuts, seeds, and whole grains that are gluten-free such as rice, quinoa, millet, and certified gluten-free oats.
  • Limit processed gluten-containing products: Many processed foods contain refined wheat, additives, and high sodium. Reducing these can ease digestive burden.
  • Gluten-free alternatives: Use certified gluten-free breads, pastas, and flours when needed. Read labels for hidden sources of wheat, barley, and rye.
  • Trial period under guidance: If your provider suspects celiac disease, keep gluten in your diet until testing is complete. If tests are negative and symptoms persist, a supervised elimination and reintroduction can help identify triggers.

Supplement and Gut Health Suggestions

  • Probiotics: Consider probiotics to support overall gut microbial balance. Choose a product with multiple strains and adequate CFU, and discuss options with your provider.
  • Digestive support: If you experience bloating or gas, digestive enzymes or targeted supports may help temporarily. Use under clinician guidance.
  • Vitamin and mineral monitoring: People with celiac disease can develop deficiencies in iron, vitamin B12, vitamin D, calcium, and folate. If you have symptoms or confirmed disease, have your provider check levels and recommend supplements as needed.

Lifestyle Recommendations

  • Stress management: Chronic stress affects gut function and the immune system. Practices such as regular sleep, mindfulness, moderate exercise, and relaxation techniques can reduce symptom severity.
  • Regular physical activity: Aim for consistent moderate activity to support digestion, immunity, and overall wellbeing.
  • Avoid cross-contact: If you follow a gluten-free diet, take steps to avoid cross-contact in shared kitchens and dining environments.
  • Food journaling: Track food intake and symptoms to help identify patterns and guide clinical evaluation.

Testing and Diagnosis

  • Serologic tests: Blood tests for specific antibodies can screen for celiac disease. These are most accurate when you are consuming gluten.
  • Genetic testing: HLA testing can identify high-risk HLA types. A negative HLA test makes celiac disease very unlikely, while a positive HLA test is not diagnostic by itself.
  • Endoscopy and biopsy: If blood tests and symptoms suggest celiac disease, an intestinal biopsy may be recommended for diagnosis.
  • Coordinate with your healthcare provider: Testing and interpretation should be done with clinical context and professional guidance.

Important Notes and Next Steps

PlexusDx provides educational information about genetic predispositions only. This report is not medical advice. If you have symptoms, abnormal test results, or concerns about gluten-related disease, consult your healthcare provider for personalized evaluation, testing, and treatment options. Do not start or stop medications or major dietary changes without professional guidance.

If you want to discuss next steps, consider sharing these results with your primary care provider, a gastroenterologist, or a registered dietitian experienced in gluten-related disorders to determine appropriate testing and a plan tailored to your needs.