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

FTO rs7195994 variant — pharmacogenetic marker of TNF inhibitor non-response, effect modulated by BMI (<27 kg/m²)

FTO rs7195994, identified through a systematic candidate SNP analysis in 519 Taiwanese RA patients receiving TNF inhibitors, remains the only independent pharmacogenetic predictor of non-response in multivariate analysis (OR 0.44, 95%CI 0.22–0.87, p=0.019). The effect is specifically observed in patients with BMI <27 kg/m² (OR 0.51, p=0.025), with no significant association at higher BMI — a novel BMI-stratified pharmacogenetic interaction for anti-TNF therapy in RA.

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FTO rs7195994 is an unexpected pharmacogenetic signal: FTO encodes a metabolism and body mass gene — an unexpected mechanistic link to anti-TNF response. The BMI interaction suggests that pharmacogenetics of biotherapies must be interpreted within their phenotypic context. Replication in European cohorts is needed before clinical implementation.