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Related Concept Videos

Graves' Disease I: Introduction01:28

Graves' Disease I: Introduction

Graves' disease is an autoimmune disorder that causes hyperthyroidism, or overactivity of the thyroid gland. It results from autoantibodies called thyroid-stimulating immunoglobulins (TSIs), which bind to thyroid-stimulating hormone (TSH) receptors, leading to overstimulation of hormone production and a hypermetabolic state.EtiologyAlthough considered idiopathic, Graves’ disease has well-established contributing factors. There is a strong genetic component, with increased prevalence in...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Selectins01:25

Selectins

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
Graves Disease II: Pathophysiology01:24

Graves Disease II: Pathophysiology

Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...

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L-selectin gene polymorphisms in Graves' disease.

Hao-Yan Chen1, Bin Cui, Shu Wang

  • 1Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Clinical Endocrinology
|May 1, 2007
PubMed
Summary

L-selectin gene polymorphisms are linked to Graves' disease (GD) susceptibility in Chinese individuals. Specific L-selectin variants, including the -642T allele and c.725C allele, were more frequent in GD patients, suggesting a genetic role.

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Area of Science:

  • Immunogenetics
  • Autoimmune Diseases
  • Molecular Biology

Background:

  • Graves' disease (GD) is an autoimmune disorder with a known genetic component.
  • L-selectin plays a role in leukocyte-endothelial interactions and inflammation.
  • Elevated soluble L-selectin levels are observed in untreated GD patients.

Purpose of the Study:

  • To investigate the association between L-selectin gene polymorphisms and Graves' disease susceptibility.
  • To determine if specific L-selectin single nucleotide polymorphisms (SNPs) are risk factors for GD in the Chinese population.

Main Methods:

  • Genotyping of two L-selectin SNPs (-642 promoter polymorphism and Pro213Ser exon 6 polymorphism) using PCR-restriction fragment length polymorphism (PCR-RFLP).
  • Study included 230 Chinese GD patients and 208 healthy controls.
  • Haplotype analysis was performed to examine combinations of polymorphisms.

Main Results:

  • A significant increase in the -642T allele frequency was observed in GD patients compared to controls (70% vs. 62%, P=0.0126).
  • The c.725C allele in exon 6 was also more frequent in GD patients.
  • Haplotype analysis revealed a significant decrease in the -642C/c.725T haplotype in GD patients (26% vs. 34%, P=0.0095).

Conclusions:

  • L-selectin gene polymorphisms are associated with an increased susceptibility to Graves' disease in the Chinese population.
  • The identified polymorphisms may contribute to the genetic predisposition of GD.