The relative importance of genetic and environmental effects for the early stages of thyroid autoimmunity: a study of healthy Danish twins

Hansen, Pia Skov; Brix, Thomas Heiberg; Iachine, Ivan A.; Kyvik, Kirsten Ohm; Hegedűs, László

doi:10.1530/eje.1.02060

Cited by 135 publications

(109 citation statements)

References 44 publications

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“…For HT, a strong genetic susceptibility for the disease has been confirmed by family and twin studies (28,29). For PCOS patients, genetic susceptibility and familial aggregation were also shown (30,31).…”

Section: Joint Etiology and Pathogenesismentioning

confidence: 82%

“…In children and siblings of patients with HT, the risk of developing HT is increased by 32-and 21-fold, respectively, with females being more frequently affected than males (28). As shown in a study of Danish twins, 73% of the susceptibility for the development of thyroid autoantibodies can be attributable to genetic factors (29). Several genes are known to be associated with the disease occurrence, progression, and severity.…”

Section: Susceptibility and Candidate Genesmentioning

confidence: 99%

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MECHANISMS IN ENDOCRINOLOGY: Thyroid and polycystic ovary syndrome

Gaberšček

Zaletel

Schwetz

et al. 2015

European Journal of Endocrinology

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Thyroid disorders, especially Hashimoto's thyroiditis (HT), and polycystic ovary syndrome (PCOS) are closely associated, based on a number of studies showing a significantly higher prevalence of HT in women with PCOS than in controls. However, the mechanisms of this association are not as clear. Certainly, genetic susceptibility contributes an important part to the development of HT and PCOS. However, a common genetic background has not yet been established. Polymorphisms of the PCOS-related gene for fibrillin 3 (FBN3) could be involved in the pathogenesis of HT and PCOS. Fibrillins influence the activity of transforming growth factor beta (TGFb). Multifunctional TGFb is also a key regulator of immune tolerance by stimulating regulatory T cells (Tregs), which are known to inhibit excessive immune response. With lower TGFb and Treg levels, the autoimmune processes, well known in HT and assumed in PCOS, might develop. In fact, lower levels of TGFb1 were found in HT as well as in PCOS women carrying allele 8 of D19S884 in the FBN3 gene. Additionally, vitamin D deficiency was shown to decrease Tregs. Finally, high estrogen-to-progesterone ratio owing to anovulatory cycles in PCOS women could enhance the immune response. Harmful metabolic and reproductive effects were shown to be more pronounced in women with HT and PCOS when compared with women with HT alone or with controls. In conclusion, HT and PCOS are associated not only with respect to their prevalence, but also with regard to etiology and clinical consequences. However, a possible crosstalk of this association is yet to be elucidated.

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Section: Joint Etiology and Pathogenesismentioning

confidence: 82%

Section: Susceptibility and Candidate Genesmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Thyroid and polycystic ovary syndrome

Gaberšček

Zaletel

Schwetz

et al. 2015

European Journal of Endocrinology

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“…Environmental factors play also an important role in the development of AITD, as the concordance rate for AITD in monozygotic twins is not 100% (27,28). Twin studies suggest that genetic factors account for about 70% of the risk of developing AITD leaving about 30% for the environmental factors (27)(28)(29)(30). Identified environmental factors are iodine intake, smoking, stress, pregnancy, estrogens, and possibly infections.…”

Section: Discussionmentioning

confidence: 99%

Natural history of the transition from euthyroidism to overt autoimmune hypo- or hyperthyroidism: a prospective study

Effraimidis¹,

Strieder²,

Tijssen

et al. 2011

European Journal of Endocrinology

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Objective: To evaluate the progression in time from euthyroidism to overt autoimmune hypothyroidism or to overt autoimmune hyperthyroidism. Subjects and methods: The design is that of a nested case-control study within the prospective Amsterdam autoimmune thyroid disease (AITD) cohort study in which 790 healthy euthyroid women with at least one first or second degree relative with documented AITD were followed for 5 years. Thyroid function tests were assessed annually. Contrast between cases (overt hypothyroidism -TSHO 5.7 mU/l and free thyroxine (FT 4 )!9.3 pmol/l and overt hyperthyroidism -TSH!0.4 mU/l and FT 4 O20.1 pmol/l, also referred to as events) and controls (matched for age and duration of follow-up). Results: At baseline, the 38 hypothyroid cases had already higher TSH and lower FT 4 concentrations than their 76 controls, and the difference between both the groups persisted 1 year before occurrence of the event. In contrast, neither TSH nor FT 4 values differed between the 13 hyperthyroid cases and their 26 controls at baseline or 1 year before the event. The prevalence of thyroid peroxidase-Ab was higher in both hypothyroid and hyperthyroid cases than in controls. At the time of event, hypothyroid cases were less common among current smokers (PZ0.083) and more common in the postpartum period (PZ0.006) than their controls, whereas hyperthyroid cases were pregnant more frequently (PZ0.063). Conclusions: The data suggest that progression toward overt autoimmune hypothyroidism is a gradual process taking several years, but in contrast overt autoimmune hyperthyroidism develops faster in terms of months.

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“…Genetic factors have been shown to strongly influence the development of autoimmune thyroid disease in twins but the impact of specific genes is still poorly understood (19). The most consistently found genes are HLA class II, CTLA4, PTPN22 and Thyrotropin receptor.…”

Section: Discussionmentioning

confidence: 99%