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Updated: May 7, 2026

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FTO rs7195994 Is associated with TNF inhibitor response in lean rheumatoid arthritis patients: A BMI-stratified

Yi-Ting Li1, I-Chieh Chen2,3, Hui-Wen Yang2

  • 1Department of Post-Baccalaureate Medicine, College of Medicine, National Chung-Hsing University, Taichung, Taiwan.

The Pharmacogenomics Journal
|May 5, 2026
PubMed

Insights

Tumor necrosis factor inhibitors (TNFi) are crucial for rheumatoid arthritis (RA) but often ineffective. The FTO rs7195994 genetic variant predicts TNFi non-response, especially in patients with lower BMI, aiding personalized RA treatment.

Area of Science:

  • Pharmacogenetics
  • Rheumatology
  • Genetics

Background:

  • Tumor necrosis factor inhibitors (TNFi) have revolutionized rheumatoid arthritis (RA) treatment.
  • However, a significant portion of RA patients (up to 40%) do not respond adequately to TNFi therapy.
  • Current clinical predictors for TNFi response are insufficient, necessitating the identification of pharmacogenetic biomarkers.

Purpose of the Study:

  • To investigate genetic variants associated with TNFi treatment response in RA patients.
  • To specifically examine the influence of body mass index (BMI) on the relationship between genetic variants and TNFi response.
  • To identify novel pharmacogenetic markers for predicting TNFi non-response in RA.

Main Methods:

  • A real-world cohort of 519 RA patients from the Taiwan Precision Medicine Initiative (TPMI) was analyzed.
  • Genotyping data for 97 candidate single nucleotide polymorphisms (SNPs) previously linked to TNFi response were examined.
  • Univariable and multivariable logistic regression models, including BMI-stratified subgroup analyses, were employed.

Main Results:

  • Three variants (FTO rs7195994, ZNF618 rs16911006, LOC105375523 rs834811) showed initial associations with TNFi response.
  • In multivariable analysis, only FTO rs7195994 remained a significant independent predictor of TNFi non-response (OR 0.44, p=0.019).
  • Among patients with BMI < 27 kg/m², the rs7195994 risk allele carriers had a 49% lower likelihood of treatment response (OR 0.51, p=0.0249), with no significant association in higher BMI groups.

Conclusions:

  • FTO rs7195994 is identified as a novel pharmacogenetic marker for TNFi non-response in RA.
  • The effect of FTO rs7195994 on TNFi response is modulated by BMI.
  • Integrating BMI-stratified genetic profiling may enhance precision medicine strategies for RA by identifying non-responders early.

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