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How SERPINA7 (TBG) Variants Affect Thyroid Health and Fertility

The thyroid gland makes hormones that regulate metabolism, energy, temperature, and reproductive function. Most thyroid hormone in blood is bound to carrier proteins. Thyroxine binding globulin or TBG is the main carrier for the hormones T4 and T3. The SERPINA7 gene encodes TBG. Variations in SERPINA7 can change TBG levels, which alters the balance between bound and free thyroid hormones. That can affect how standard lab tests look and how your body senses thyroid hormone.

Why TBG Matters

  • TBG binds and transports T4 and T3 in the bloodstream.
  • Lower TBG means less hormone is carried in the bound reserve, which can lower total T4 and T3 lab values while leaving free, active hormone unchanged.
  • Misinterpretation of total thyroid hormone tests can lead to unnecessary treatment or missed diagnoses.
  • TBG changes can influence symptoms such as fatigue, weight change, temperature intolerance, menstrual irregularity, and fertility challenges.

What You Can Do

PlexusDx provides genetic information to help you and your healthcare team interpret test results. This article is educational and not medical advice. Always consult your healthcare provider before changing medications, supplements, or lifestyle based on genetic results.

Nutritional and Lifestyle Considerations

  • Iodine supports thyroid hormone synthesis. Use iodized salt or iodine-rich foods if your diet is low in iodine.
  • Selenium supports thyroid hormone conversion and antioxidant protection. Include selenium-rich foods such as Brazil nuts, seafood, and whole grains; supplements may be considered with clinician guidance.
  • Vitamin A is important for thyroid hormone signaling. Eat colorful fruits and vegetables and consider intake if you have restricted diets.
  • Zinc and iron are needed for thyroid hormone production and function. Address deficiencies through diet or supplements as advised by your provider.
  • Moderate soy and cruciferous vegetables if you have dietary patterns that could interfere with thyroid function, especially in the context of low iodine.
  • Maintain a balanced diet, regular physical activity, healthy sleep, and manage stress to support endocrine health.
  • Avoid or reduce exposure to environmental hormone disruptors such as certain plastics, pesticides, and smoking.

Testing and Monitoring

  • When SERPINA7 variants suggest altered TBG, request both total and free thyroid hormone measurements and TSH from your clinician.
  • Consider direct TBG measurement if labs show unexpectedly low total hormones with normal free hormones or clinical suspicion of TBG deficiency.
  • Keep a symptom log including energy, weight, temperature tolerance, menstrual cycle patterns, and fertility concerns to share with your clinician.

Genetic Interpretation for rs28933689

2 effect alleles (TT)

You carry two copies of the effect allele at rs28933689. This pattern is associated with thyroxine binding globulin deficiency. Lower TBG levels can reduce total T4 and T3 values on laboratory tests while free hormone levels may remain normal. That can create diagnostic confusion and has potential effects on metabolism, energy levels, menstrual cycles, and reproductive health.

What to expect

  • Possible low total T4 and T3 with normal free T4 and free T3.
  • Symptoms may include fatigue, weight changes, temperature sensitivity, or menstrual irregularities in women.
  • Fertility may be affected indirectly if thyroid function is not accurately assessed or managed.

Practical steps

  • Ask your healthcare provider to measure free and total T4 and T3, TSH, and TBG when interpreting thyroid function.
  • Monitor symptoms and discuss whether direct TBG measurement is appropriate.
  • Optimize intake of iodine, selenium, vitamin A, zinc, and iron through diet or under medical supervision via supplementation.
  • Limit unnecessary exposure to environmental hormone disruptors.
  • Work with your clinician if you are trying to conceive to ensure thyroid tests reflect your true hormone status.
1 effect allele (AT)

You carry one copy of the effect allele at rs28933689. This genotype is associated with likely reduced TBG levels. Reduced TBG can lead to lower total thyroid hormone levels on standard labs while free hormone levels remain in the normal range. That may complicate interpretation of thyroid status and relate to symptoms such as changes in energy, weight, and menstrual regularity.

What to expect

  • Possible mild reduction in total T4 and T3 with normal free hormone measurements.
  • Symptoms may be mild or absent, but remain alert to fatigue, weight shifts, or irregular cycles.

Practical steps

  • Request free and total T4 and T3 plus TSH when getting thyroid labs.
  • Discuss TBG testing with your clinician if lab results are inconsistent with how you feel.
  • Support thyroid health with sufficient iodine, selenium, vitamin A, zinc, and iron through diet or clinician-guided supplements.
  • Monitor reproductive health and consult your provider if you have fertility concerns.
0 effect alleles (AA)

You carry two copies of the non-effect allele at rs28933689. This is the common genotype and indicates expected TBG function. Your SERPINA7 gene likely produces normal TBG levels so the balance between bound and free thyroid hormones should be typical. Standard thyroid tests are more likely to reflect true thyroid status in the usual way.

What to expect

  • Standard relationships between total and free thyroid hormone levels are expected.
  • No increased genetic risk for TBG deficiency from this variant.

Practical steps

  • Continue routine thyroid monitoring as recommended by your clinician, especially if symptoms arise.
  • Support thyroid and reproductive health with a balanced diet that includes iodine, selenium, vitamin A, zinc, and iron.
  • Maintain healthy lifestyle habits to support overall endocrine health.

Supplement Notes

  • Selenium: often used to support thyroid conversion and antioxidant defense. Typical supplemental doses are small and should be supervised by a clinician to avoid excess.
  • Myo-inositol: sometimes used in reproductive health and metabolic conditions that affect ovulation and thyroid interplay. Discuss use with your provider.
  • Vitamin D: supports immune and reproductive health. Test levels and supplement under guidance if deficient.

When to Talk to Your Healthcare Provider

  • If lab tests show low total T4 or T3 but normal TSH and free hormones.
  • If you have symptoms such as unexplained fatigue, changes in weight, menstrual irregularity, or difficulty conceiving.
  • Before starting supplements or making major dietary changes.
  • When you want targeted testing such as TBG concentration or specialized endocrine evaluation.

PlexusDx provides educational genetic information only. This content is not medical advice. Always consult your healthcare provider to interpret genetic results, guide testing, and make decisions about supplements, diet, or treatment.