Association of genetic polymorphisms in the type II deiodinase gene with bipolar disorder in a subset of Chinese population

He, Bing; Li, Junyan; Wang, Gang; Ju, Weina; Lu, Yinan; Shi, Yongyong; He, Lin; Zhong, Nanbert

doi:10.1016/j.pnpbp.2009.05.003

Cited by 42 publications

(35 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Open reading frame a (ORFa) is the site among the three short ORFs primarily responsible for the inhibitory effect of this 59-untranslated region SNP on D2 translation (62). Genotypes 3Gly-3Gly, 92Ala-92Ala, as well as the haplotype ORFa-3Gly-92Ala, decrease D2 enzymatic activity, alter absolute and relative T3 and T4 levels, and contribute to the pathogenesis of neurologic disease (23,62), suggesting that other functional genetic variants of DIO2 other than Thr92Ala may be involved. Our results do not provide strong support for rs12885300 (ORFa-Gly3Asp) in ALI susceptibility given the nominal significance of association individually among AAs and when combined into haplotypes (92Ala-ORFa-3Gly) in EAs.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, D2 has been suggested to regulate locally TH signaling in a tissueand time-specific fashion, independently of TH serum concentrations (20). Although TH metabolizing genes have not yet been explored in the context of sepsis or ALI, DIO2 variants are associated with multiple disorders, including bipolar disorder, diabetes, osteoarthritis, and mental retardation (21)(22)(23)(24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Type 2 Deiodinase and Host Responses of Sepsis and Acute Lung Injury

Fan

Xie

Pino-Yanes

et al. 2011

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

The role of thyroid hormone metabolism in clinical outcomes of the critically ill remains unclear. Using preclinical models of acute lung injury (ALI), we assessed the gene and protein expression of type 2 deiodinase (DIO2), a key driver for synthesis of biologically active triiodothyronine, and addressed potential association of DIO2 genetic variants with ALI in a multiethnic cohort. DIO2 gene and protein expression levels in murine lung were validated by microarrays and immunoblotting. Lung injury was assessed by levels of bronchoalveolar lavage protein and leukocytes. Single-nucleotide polymorphisms were genotyped and ALI susceptibility association assessed. Significant increases in both DIO2 gene and D2 protein expression were observed in lung tissues from murine ALI models (LPS-and ventilator-induced lung injury), with expression directly increasing with the extent of lung injury. Mice with reduced levels of DIO2 expression (by silencing RNA) demonstrated reduced thyroxine levels in plasma and increased lung injury (increased bronchoalveolar lavage protein and leukocytes), suggesting a protective role for DIO2 in ALI. The G (Ala) allele of the Thr92Ala coding single-nucleotide polymorphism (rs225014) was protective in severe sepsis and severe sepsis-associated ALI after adjustments for age, sex, and genetic ancestry in a logistic regression model in European Americans. Our studies indicate that DIO2 is a novel ALI candidate gene, the nonsynonymous Thr92Ala coding variant of which confers ALI protection. Increased DIO2 expression may dampen the ALI inflammatory response, thereby strengthening the premise that thyroid hormone metabolism is intimately linked to the integrated response to inflammatory injury in critically ill patients.Keywords: acute respiratory distress syndrome; hypothyroidism; mechanical ventilation; sepsis Acute lung injury (ALI) is one of the major causes of acute respiratory failure that usually develops in response to major insults, such as sepsis, trauma, pneumonia, and multiple transfusions (1). Although mechanical ventilation (MV) is indispensable for the survival of patients with ALI (2), clinical trials have shown that improperly delivered MV causes or worsens lung injury, a syndrome known as ventilator-induced lung injury (VILI). ALI and VILI are characterized by augmented capillary leakage, acute inflammation, and increases in inflammatory cytokine expression (3, 4). Microarray analyses have identified a number of ALI-associated candidate genes correlated with the outcome of both ALI and VILI (5-8). Case-control association studies further support that genetic variants in these genes contribute to susceptibility and survival of sepsis and ALI (8-12). Despite these increasing insights into ALI/VILI pathobiology, ALI continues to carry an unacceptably high mortality (.30%), and the basis for the increased ALI morbidity/mortality remains poorly understood.Clinicians have had a long-standing interest in the enigmatic role of thyroid hormones (THs) in critically ill patients (13) who e...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Type 2 Deiodinase and Host Responses of Sepsis and Acute Lung Injury

Fan

Xie

Pino-Yanes

et al. 2011

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…In the Chinese Han population, He et al (46) found that the D2-ORF a -Gly3Asp variant and D2-92Ala variant were linked to higher risk for bipolar mood disorder.…”

Section: Cognitive Function and Affective Disordersmentioning

confidence: 99%

GENETICS IN ENDOCRINOLOGY: Genetic variation in deiodinases: a systematic review of potential clinical effects in humans

Verloop

Dekkers

Peeters

et al. 2014

European Journal of Endocrinology

View full text Add to dashboard Cite

Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation.

show abstract

“…In agreement, in vitro studies suggested that D2-rs1288530 polymorphism leads to higher activity of D2 at the pituitary level (Coppotelli et al, 2006). In a long case-control Chinese study, the haplotypes ORFa-3Asp-92Ala and ORFa-3Gly-92Ala indicated higher susceptibility for bipolar disorders, while ORFa-3Asp-92Thr probably played a protective role (He et al, 2009). According to this evidence, it is feasible that variants of D2 gene can produce "brain hypothyroidism" limiting T3 action on CNS affecting brain neurotransmission.…”

Section: Association Between Deionidase Polymorphisms and Thyroid Hormentioning

confidence: 75%