The Association of Polymorphisms in the Type 1 and 2 Deiodinase Genes with Circulating Thyroid Hormone Parameters and Atrophy of the Medial Temporal Lobe

Jong, Frank Jan de; Peeters, Robin P.; Heijer, Tom den; Deure, Wendy M van der; Hofman, Albert; Uitterlinden, André G.; Visser, Theo J.; Breteler, Monique M.B.

doi:10.1210/jc.2006-1331

Cited by 97 publications

(80 citation statements)

References 26 publications

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“…hapmap.org). Associations of these polymorphisms with serum TH levels have been reported previously (8,(10)(11)(12)20), and are replicated in our study.…”

Section: Discussionsupporting

confidence: 89%

“…At baseline, all participants were interviewed and underwent physical examination. Serum TSH, FT 4 (chemoluminescence assay; Vitros, ECI Immunodiagnostic System, Ortho-Clinical Diagnostics, Rochester, NY, USA), and TPOAb (immunometric assay; DPC) levels were determined in 854 subjects of whom DNA was available (8). After applying exclusion criteria, 697 subjects were included in the present study.…”

Section: Study Populationsmentioning

confidence: 99%

“…The causative genes are, however, not well established. Well-known TH pathway genes such as the deiodinases (8)(9)(10)(11)(12), TSH receptor (10,13,14) and TH transporters (15)(16)(17) have been associated with TH serum levels, but their contribution to the overall variation is modest (12,13). A genome-wide linkage scan by Panicker et al (18) identified eight chromosomal loci involved in the control of the pituitarythyroid axis, but as can be expected from this type of study, the actual genes were not identified.…”

Section: Introductionmentioning

confidence: 96%

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A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels

Medici¹,

Deure²,

Verbiest³

et al. 2011

European Journal of Endocrinology

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Objective: Minor variation in serum thyroid hormone (TH) levels can have important effects on various clinical endpoints. Although 45-65% of the inter-individual variation in serum TH levels is due to genetic factors, the causative genes are not well established. We therefore studied the effects of genetic variation in 68 TH pathway genes on serum TSH and free thyroxine (FT 4 ) levels. Design and methods: Sixty-eight genes (1512 polymorphisms) were studied in relation to serum TSH and FT 4 levels in 1121 Caucasian subjects. Promising hits (P!0.01) were studied in three independent Caucasian populations (2656 subjects) for confirmation. A meta-analysis of all four studies was performed. Results: For TSH, eight PDE8B polymorphisms (PZ4!10 K17 ) remained significant in the metaanalysis. For FT 4 , two DIO1 (PZ8!10 K12 ) and one FOXE1 (PZ0.0003) polymorphisms remained significant in the meta-analysis. Suggestive associations were detected for one FOXE1 (PZ0.0028) and three THRB (PZ0.0045) polymorphisms with TSH, and one SLC16A10 polymorphism (PZ0.0110) with FT 4 , but failed to reach the significant multiple-testing corrected P value (P!0.0022 and P!0.0033 respectively). Conclusions: Using a large-scale association analysis, we replicated previously reported associations with genetic variation in PDE8B, THRB, and DIO1. We demonstrate effects of genetic variation in FOXE1 on serum FT 4 levels, and borderline significant effects on serum TSH levels. A suggestive association of genetic variation in SLC16A10 with serum FT 4 levels was found. These data provide insight into the molecular basis of inter-individual variation in TH serum levels.

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“…hapmap.org). Associations of these polymorphisms with serum TH levels have been reported previously (8,(10)(11)(12)20), and are replicated in our study.…”

Section: Discussionsupporting

confidence: 89%

Section: Study Populationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels

Medici¹,

Deure²,

Verbiest³

et al. 2011

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Metaanalysis method is notoriously prone to publication bias, and although we have attempted to trace unpublished observations, we cannot assure that small negative studies were overlooked. Moreover, one of the identified studies was not included in this metaanalysis because data regarding diabetic population was unextractable (40).…”

Section: Discussionmentioning

confidence: 99%

Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case–control study and meta-analysis

Dora¹,

Machado²,

Rheinheimer³

et al. 2010

European Journal of Endocrinology

124

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Objective: The type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T 3 ) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2. Design and methods: A case-control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms 'rs225014' odds ratio (OR) 'thr92ala' OR 'T92A' OR 'dio2 a/g'. Results: In the case-control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (nZ173) versus 12.0% (nZ62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03-1.94, PZ0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78-2.51)), Grarup (OR 1.09 (95% CI 0.92-1.29)), and Maia (OR 1.22 (95% CI 0.78-1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03-1.36, PZ0.02). Conclusions: Our results indicate that in a case-control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a metaanalysis including 11 033 individuals, and support a role for intracellular T 3 concentration in skeletal muscle on DM2 pathogenesis.

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“…The effect of two polymorphisms in D1 gene, D1-rs11206244 (D1-C785T) and D1-rs12095080 (D1-A1814G) on thyroid hormone metabolism has been evaluated in randomly selected subjects (Peeters et al, 2003). The allele T of D1-rs11206244 was associated with high levels of rT3 and high rT3/T4 ratio and a low T3/rT3 in plasma; whereas the G allele of D1-A1814G was associated with a high T3/rT3 (de Jong et al, 2007;Peeters et al, 2003). These results suggest a lower activity in T carriers of rs11206244 than G carriers (Peeters et al, 2003).…”

Section: Association Between Deionidase Polymorphisms and Thyroid Hormentioning

confidence: 99%

Depressive Disorders and Thyroid Function

Araya¹,

Massardo²,

Fiedler³

et al. 2012

Thyroid and Parathyroid Diseases - New Insights Into Some Old and Some New Issues

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The Association of Polymorphisms in the Type 1 and 2 Deiodinase Genes with Circulating Thyroid Hormone Parameters and Atrophy of the Medial Temporal Lobe

Cited by 97 publications

References 26 publications

A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels

A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels

Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case–control study and meta-analysis

Depressive Disorders and Thyroid Function

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