rs180223

badMag 3.0

This is a variant in the TG gene that changes a serine to an alanine.

Key Literature Trait Associations

Autoimmune Thyroid Disease Susceptibility

Ban et al. (2003) originally identified the TG exon 10 SNP cluster containing rs180223 as significantly associated with autoimmune thyroid disease (AITD) in a sequencing study of all 48 TG exons. However, a subsequent meta-analysis of 3,013 AITD cases and 1,812 controls (2018) found no significant overall association between rs180223 and AITD risk, suggesting the effect may be population-specific or driven by LD with other TG variants.

Ban Y et al. “Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease.” Proceedings of the National Academy of Sciences of the United States of America 100(25):15119-15124 (2003)

Allele G

OR —

p 1.0e-3

Candidate gene study

Zhang ML et al. “Association between thyroglobulin polymorphisms and autoimmune thyroid disease: a systematic review and meta-analysis of case-control studies.” Genes and Immunity (2019)

Allele G

OR —

p —

N 4,825

Meta-analysis

multi-ancestry

Tomer Y et al. “Thyroglobulin is a thyroid specific gene for the familial autoimmune thyroid diseases.” The Journal of Clinical Endocrinology and Metabolism (2002)

Allele G

OR 1.40

p 5.0e-2

N 358

Candidate gene study

European

Differentiated Thyroid Cancer Risk

rs180223 encodes the Ser734Ala (c.2200T>G) substitution in exon 10 of the thyroglobulin (TG) gene. In a case-control study of 309 DTC patients and 512 controls, variants in the TG exon 10-12 cluster including rs180223 were associated with increased differentiated thyroid cancer risk under a dominant model (OR 1.80, P = 0.001). Thyroglobulin is the precursor protein for thyroid hormones and the primary autoantigen in autoimmune thyroid disease.

Akdi A et al. “Common variants of the thyroglobulin gene are associated with differentiated thyroid cancer risk.” Thyroid : Official Journal of the American Thyroid Association 21(5):519-525 (2011)

Allele G

OR 1.80

p 1.0e-3

Candidate gene study

Matakidou A et al. “Risk of non-medullary thyroid cancer influenced by polymorphic variation in the thyroglobulin gene.” Carcinogenesis (2004)

Allele G

OR 1.80

p —

N 704

Preliminary work

European

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ClinVar annotation

Risk Factor★★★☆

8 submitters4 publications

Autoimmune thyroid disease, susceptibility to, 3; Iodotyrosyl coupling defect (TDH3); not specified

rs180223

Key Literature Trait Associations

Autoimmune Thyroid Disease Susceptibility

Differentiated Thyroid Cancer Risk

ClinVar annotation

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