Related Experiment Videos

Influence of common non-synonymous Toll-like receptor 4 polymorphisms on bronchopulmonary dysplasia and prematurity

Pascal M Lavoie1, Mihoko Ladd, Aaron F Hirschfeld

  • 1Child & Family Research Institute of British Columbia, Vancouver, Canada. plavoie@cw.bc.ca

Plos One
|February 21, 2012
PubMed

Insights

Toll-like receptor 4 (TLR4) gene variations may slightly influence bronchopulmonary dysplasia (BPD) severity in some preterm infants. Further research is needed to understand genetic susceptibility to BPD and clinical heterogeneity.

Area of Science:

  • Genetics
  • Neonatology
  • Pulmonology

Background:

  • Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in preterm infants and a risk factor for severe respiratory syncytial virus (RSV) infection.
  • Toll-like receptor 4 (TLR4) plays a role in lung oxidative injury, and TLR4 gene polymorphisms have been linked to RSV infection.
  • The independent association of TLR4 polymorphisms with BPD or prematurity remains unclear, potentially confounded by these conditions.

Purpose of the Study:

  • To investigate whether TLR4 polymorphisms Asp299Gly (rs4986790) and Thr399Ile (rs4986791) are independently associated with BPD or premature birth.
  • To analyze these associations in two distinct population-based cohorts of preterm infants at risk for BPD and term-matched infants.

Main Methods:

  • Analysis of two population-based cohorts: Canadian (n=269) and Finnish (n=434) preterm infants.
  • Genotyping for TLR4 polymorphisms Asp299Gly and Thr399Ile.
  • Statistical adjustment for covariates including twins, ethnicity, gestational age, birth weight, and gender.

Main Results:

  • In the Canadian cohort, the TLR4-299 heterozygous genotype was significantly under-represented in infants without BPD (p=0.014).
  • This association was not replicated in the Finnish cohort, which had a lower BPD incidence.
  • No significant association (>2-fold) was detected between TLR4 genotypes and prematurity (p>0.05).

Conclusions:

  • TLR4 genotypes may have a modest influence on BPD severity in specific populations of high-risk preterm infants.
  • The findings suggest that clinical heterogeneity might impact genetic susceptibility to BPD.
  • Further studies are warranted to elucidate the role of TLR4 in BPD pathogenesis.

Related Concept Videos

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...
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...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

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...
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features01:24

Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features

Chronic bronchitis is a key phenotype of chronic obstructive pulmonary disease (COPD), characterized by airway-centered inflammation and mucus overproduction. It develops from long-term exposure to harmful particles or gases, most commonly cigarette smoke, which triggers a persistent inflammatory response.Cellular and Structural ChangesInflammation initially affects the large bronchi and later the smaller airways, with infiltration by immune cells, including neutrophils, macrophages, and...