Genetic Factors in Thyroid Hormone Resistance
Author Information
Author(s): Alberobello Anna Teresa, Congedo Valentina, Liu Hong, Cochran Craig, Skarulis Monica C, Forrest Douglas, Celi Francesco S
Primary Institution: NIDDK-NIH
Hypothesis
Polymorphisms in the human intron control region of the THRB gene could modulate the pituitary expression of the mutated gene contributing to the clinical presentation of resistance to thyroid hormone.
Conclusion
The study illustrates how a combination of a coding mutation and non-coding SNPs can lead to a tissue-specific dominant-negative condition in thyroid hormone resistance.
Supporting Evidence
- The index case of pituitary-selective resistance is characterized by the missense R338W mutation in cis with two common SNPs.
- Reporter gene assays indicated that the rs2596623T SNP increases pituitary cell-specific activity of the TR β2 promoter.
- The study found that the combined coding mutation and non-coding SNPs create a dominant-negative condition affecting thyroid hormone response.
Takeaway
Some people have a condition where their body doesn't respond properly to thyroid hormone, and this study found that specific genetic changes can make this problem worse.
Methodology
Screening and in vitro characterization of polymorphisms of the intron enhancer region of the THRB gene.
Limitations
The study's findings may not be generalizable due to the small sample size and the lack of genetic material from relatives for haplotype determination.
Participant Demographics
The study involved 45 patients with resistance to thyroid hormone, categorized as either generalized or pituitary-selective resistance.
Statistical Information
P-Value
p<0.0001
Statistical Significance
p<0.0001
Digital Object Identifier (DOI)
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