Background:Transcription factor 7-like 2 (TCF7L2)-rs7903146 polymorphism is associated with increased risk of type 2 diabetes.The response of insulin and insulin resistance to artichoke leaf extract (ALE) may be affected by TCF7L2-rs7903146 polymorphism.Objective:This study examined the effects of ALE supplementation on metabolic parameters of the TCF7L2-rs7903146 polymorphism in patients with metabolic syndrome (MetS).Design,setting,participants and interventions:This double-blind clinical trial was conducted on 80 patients with MetS in Sina Clinic,Khoy,Iran.The patients were randomized into ALE or placebo groups to receive either ALE (1800 mg/d as four tablets) or matching placebo for 12 weeks.Main outcome measures:Anthropometric indices,blood pressure,glucose and lipid profile levels were measured before and after the study.Moreover,patients were genotyped for TCF7L2 polymorphism.Results:ALE supplementation decreased insulin level and the homeostasis model assessment of insulin resistance (HOMA-IR) in patients with the TT genotype of TCF7L2-rs7903146 polymorphism (P ＜ 0.05).There was no significant interaction between blood pressure,glucose and lipid profile response to ALE supplementation.Conclusion:The responses ofinsulin and HOMA-IR to ALE supplementation have shown an interaction with single-nucleotide polymorphism rs7903146 in TCF7L2.Trial registration:Iranian Registry of Clinical Trial IRCT201409033320N9.