The Role of Vitamin D Receptor Gene Polymorphisms in Thyroid-Associated Orbitopathy

Maciejewski, Adam; Kowalczyk, Michał; Gasińska, T; Szeliga, Anna; Prendecki, Michał; Dorszewska, Jolanta; Żaba, Ryszard; Łącka, Katarzyna

doi:10.1080/09273948.2019.1629605

Cited by 7 publications

(7 citation statements)

References 55 publications

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“…25,26 Data on PAI-1 polymorphisms in TED, up till now, have not been published, and only few candidate other genes have been studied in this respect. CTLA-4, 27 vitamin D receptor, 28 TNF, IL-10 29 and deiodinase-2 polymorphisms 30 were recently described in patient cohorts of comparable size. However, unlike these genes which are immune response related, PAI-1 acts on the other side of the orbital process, stabilizing the extracellular matrix and facilitating its expansion, which explains nearly all signs and symptoms of TED.…”

Section: Discussionmentioning

confidence: 96%

The 4G/5G Polymorphism of Plasminogen Activator Inhibitor Type 1 is a Predictor of Moderate-to-Severe Thyroid Eye Disease

Katkó¹,

Galgoczi²,

Erdei³

et al. 2021

JIR

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Introduction Thyroid eye disease (TED) is an autoimmune disease of the orbits. Once developed, complete cure is rare. Plasminogen activator inhibitor type 1 (PAI-1) contributes to remodeling of connective tissue and has a central role in the pathogenesis of TED. We aimed to test if the 4G/5G polymorphism of PAI-1 is a predictor of the development of moderate-to-severe TED. Methods A total of 185 patients with Graves’ disease, 87 of them with TED, 98 without TED, as well as 201 healthy controls, were studied. Genomic DNA was isolated from peripheral blood samples. The 4G/5G polymorphism of the PAI-1 gene was analyzed by allele-specific PCR, and the distribution of genotypes was calculated in each group. Plasma PAI-1 and thyroid hormone levels were measured by ELISA and ECLIA, respectively. Results The 4G/4G genotype was associated with the development of moderate-to-severe TED (OR = 2.54; 95% CI: 1.26–5.14; p < 0.01). The 4G/5G polymorphism of PAI-1 was not a predictor of plasma PAI-1 levels. Conclusion The 4G/4G genotype of PAI-1 is a risk factor for the development of moderate-to-severe TED. Patients with Graves’ disease who harbor this genotype may be candidates for special attention towards the development of TED.

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Section: Discussionmentioning

confidence: 96%

The 4G/5G Polymorphism of Plasminogen Activator Inhibitor Type 1 is a Predictor of Moderate-to-Severe Thyroid Eye Disease

Katkó¹,

Galgoczi²,

Erdei³

et al. 2021

JIR

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“…Research efforts are now directed toward identifying characteristics, including gene polymorphisms, which could modify the risk of TED and be associated with its occurrence; these could be used to facilitate early diagnosis. Maciejewski et al (2020) found a C gene polymorphism rs2228570 ( Fok I) in VDR to occur more frequently in patients compared to unaffected subjects; this may be a risk factor contributing to the development of TED in patients of Caucasian origin with Graves’ disease [ 190 ].…”

Section: Vitamin D Vdr and Calcitriol Analogues In Ocular Diseasesmentioning

confidence: 99%

Vitamin D, the Vitamin D Receptor, Calcitriol Analogues and Their Link with Ocular Diseases

Caban

Lewandowska

2022

Nutrients

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The global prevalence of eye diseases continues to grow, bringing with it a reduction in the activity levels and quality of life of patients, and partial or complete blindness if left untreated. As such, there is considerable interest in identifying more effective therapeutic options and preventive agents. One such agent is vitamin D, known to have a range of anti-cancer, anti-angiogenic, anti-inflammatory and anti-oxidative properties, and whose deficiency is linked to the pathogenesis of a range of cardiovascular, cancer, and inflammatory diseases. This review presents the current stage of knowledge concerning the link between vitamin D and its receptor and the occurrence of eye disease, as well as the influence of analogues of calcitriol, an active metabolite of vitamin D. Generally, patients affected by various ocular disorders have vitamin D deficiency. In addition, previous findings suggest that vitamin D modulates the course of eye diseases and may serve as a marker, and that its supplementation could mitigate some disorders. However, as these studies have some limitations, we recommend further randomized trials to clarify the link between vitamin D and its activity with eye disease.

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“…The authors concluded that measurement of serum 25(OH) D and 1,25(OH) 2 D with calculation of the 1,25(OH) 2 D/ 25(OH)D ratio could provide value independent of serum ACE or absolute white blood cell count for the diagnosis of presumed or probable sarcoidosis, particularly in patients where biopsy is either impossible or impractical. It is important to keep in mind, however, that in settings where the prevalence of sarcoidosis is low, the predictive value of any of serum ACE, of absolute white blood cell count, or of the 1,25 (OH) 2 D/25(OH)D ratio as surrogates of more definitive radiographic or tissue-based diagnoses of sarcoidosis will decrease dramatically.Maciejewski et al 24 studied 107 patients with thyroid-associated orbitopathy (TAO) and 130 control subjects seen at a referral center in Poznan, Poland, to determine whether polymorphisms in the vitamin D receptor (VDR) differed in their genotypic distribution across the two cohorts. The researchers used realtime polymerase chain reaction (PCR)-based testing to search for five specific VDR polymorphisms: rs2228570, rs1544410, rs7975232, rs731236, and rs11568820.…”

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confidence: 99%

“…Maciejewski et al 24 studied 107 patients with thyroid-associated orbitopathy (TAO) and 130 control subjects seen at a referral center in Poznan, Poland, to determine whether polymorphisms in the vitamin D receptor (VDR) differed in their genotypic distribution across the two cohorts. The researchers used realtime polymerase chain reaction (PCR)-based testing to search for five specific VDR polymorphisms: rs2228570, rs1544410, rs7975232, rs731236, and rs11568820.…”

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confidence: 99%

“…12 Similarly, modest reductions in the risk of developing uveitis in the setting of JIA were identified in the prospective study by Sengler et al 17 at a single tertiary referral center in Berlin, Germany, where the authors showed that JIA patients with a normal vitamin D level were less likely to develop uveitis (OR = 0.95, 95% CI 0.91-0.99); and by Sobrin et al, 16 who performed a retrospective case-control study on a health care claims database from a large private insurer in the US and found that 2790 controls without uveitis were slightly less likely to be deficient in vitamin D than the 558 identified cases with noninfectious uveitis (OR = 0.79, 95% CI 0.62-0.99). Three Original Articles [23][24][25] in this issue of Ocular Immunology & Inflammation (OII) address the role of vitamin D in ocular inflammation.…”

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Vitamin D and Ocular Inflammation

Cunningham

Sobrin

Hall

et al. 2020

Ocular Immunology and Inflammation

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The term vitamin D refers to a family of secosteroid compounds derived from cholesterol that are best known for facilitating intestinal absorption of calcium and phosphate required for normal bone development and homeostasis. There are two major forms of vitamin D: vitamin D2, known as ergocalciferol, which is derived from plants, and vitamin D3, known as cholecalciferol and which is derived from animal tissues. Humans generate vitamin D from 7dehydrocholesterol in the deep epidermis following exposure to natural ultraviolet B (UVB) radiation in sunlight. In the absence of supplementation, most vitamin D in humans is dermal in origin and dependent on adequate sunlight exposure, with more pigmented people requiring longer exposure than those who are lightly pigmented to achieve similar serum levels of vitamin D. Fatty fish and fortified foods can augment skin-based synthesis, but dietary vitamin D alone is often insufficient to achieve adequate doses. 1-6 Given indoor work-life routines and current recommendations to limit unprotected sunlight exposure, it is perhaps not surprising that billions of people around the world are believed to be vitamin D deficient, defined as a serum level of less than ≤20 ng/mL (50 nmol/L). Although accurate estimates of vitamin D deficiency are not available for most countries, 7 a survey of 4495 US citizens tested as part of a 2005-2006 National Health and Nutrition Examination Survey identified vitamin D deficiency in approximately 40% of adults, with much higher rates in Latinos (~70%) and African-Americans (~80%). 8 Rates of vitamin D deficiency in many parts of Asia, India, The Middle East, and African are believed to be in excess of 90%. 9,10 In the extreme, vitamin D deficiency results in rickets in children and osteomalacia in adults. However, increasing epidemiological evidence points to important roles for vitamin D in normal functioning of the cardiovascular, nervous, endocrine, and immune systems. In fact, a number of epidemiological studies have associated vitamin D deficiency with statistically higher rates of all-cause mortality, of cancer, and of cardiovascular, neurodegenerative, metabolic, and autoimmune diseaseincluding noninfectious uveitis and scleritis. [1][2][3][4][5][6][11][12][13][14][15][16][17][18][19][20][21][22] Specific forms of uveitis linked to vitamin D deficiency include noninfectious anterior uveitis, 18,19 anterior uveitis in the setting of juvenile idiopathic arthritis, 17 Behçet's-associated uveitis, 15,21 and uveitis in patients with Vogt-Koyanagi-Harada disease. 20,22 Of note, Chiu et al. 13 recently performed a prospective case-control study of 151 patients with noninfectious uveitis seen at two tertiary centers in Victoria, Australia, from January through August 2017. The researchers found that subjects with active uveitis tended to have lower serum vitamin D levels than patients with inactive uveitis (46 vs 64 nmol/L; p < .001), that these levels in patients with active uveitis were lower than those observed in the local non-uveitic populat...

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The Role of Vitamin D Receptor Gene Polymorphisms in Thyroid-Associated Orbitopathy

Cited by 7 publications

References 55 publications

The 4G/5G Polymorphism of Plasminogen Activator Inhibitor Type 1 is a Predictor of Moderate-to-Severe Thyroid Eye Disease

The 4G/5G Polymorphism of Plasminogen Activator Inhibitor Type 1 is a Predictor of Moderate-to-Severe Thyroid Eye Disease

Vitamin D, the Vitamin D Receptor, Calcitriol Analogues and Their Link with Ocular Diseases

Vitamin D and Ocular Inflammation

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