Related Experiment Video

Updated: Jun 9, 2026

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
07:37

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice

Published on: June 6, 2025

Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis

Lydia R Coulthard1, John C Taylor, Steve Eyre

  • 1NIHR-Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU), University of Leeds, Leeds, UK.

Annals of the Rheumatic Diseases
|September 1, 2010
PubMed
Abstract

Insights

Genetic variations in the p38 signalling network are linked to rheumatoid arthritis (RA) treatment response. Certain single nucleotide polymorphisms (SNPs) correlate with effectiveness of anti-tumour necrosis factor (TNF) therapies, particularly infliximab and adalimumab.

Area of Science:

  • Immunogenetics
  • Pharmacogenomics
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) treatment response to tumour necrosis factor (TNF) antagonists is variable.
  • Investigating genetic factors influencing anti-TNF therapy efficacy is crucial for personalized medicine.

Purpose of the Study:

  • To explore the association between genetic variations in the p38 signalling network and patient response to anti-TNF therapies in RA.
  • To identify specific single nucleotide polymorphisms (SNPs) that predict treatment outcomes.

Main Methods:

  • Genotyping of 1102 UK Caucasian RA patients receiving infliximab, adalimumab, or etanercept for 38 SNPs in 12 p38 network genes.
  • Regression analyses assessed genotype-treatment response correlation using DAS28 and EULAR criteria at 6 months.
  • Stratified analyses examined associations with individual anti-TNF agents.

Main Results:

  • Seven SNPs in five genes within the p38 network were associated with improved DAS28 scores, collectively explaining 3% of outcome variance.
  • SNPs in genes encoding upstream (MKK6) and downstream (MAPKAPK2, MSK1, MSK2) proteins, and p38-α MAPK (MAPK14), showed associations.
  • One SNP (rs2716191 in MAP2K6) correlated with EULAR response; associations were stronger for infliximab and adalimumab than etanercept.

Conclusions:

  • The p38 signalling network contains SNPs associated with anti-TNF response in RA, particularly for infliximab and adalimumab.
  • These genetic markers may contribute to predicting treatment efficacy.
  • Independent cohort validation is recommended to confirm these pharmacogenetic findings.

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...